1.
Neuroplasticity of sensory and sympathetic nerve fibers in the painful arthritic joint.
Source
Research Service, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA.
Abstract
OBJECTIVE.: Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization. METHODS.: A painful arthritic knee joint was produced by injection of complete Freund's adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages). RESULTS.: In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68(+) macrophages, CD31(+) blood vessels, CGRP(+) , NF200(+) , GAP43(+) , and TH(+) nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31(+) blood vessels or CD68(+) macrophages. CONCLUSIONS.: Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain.
Copyright © 2012 by the American College of Rheumatology.
Depletion of B2 but Not B1a B Cells in BAFF Receptor-Deficient ApoE Mice Attenuates Atherosclerosis by Potently Ameliorating Arterial Inflammation.
Source
Vascular Biology and Atherosclerosis Laboratory, Baker IDI Heart and Diabetes Institute, Victoria, Australia.
Abstract
We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE(-/-) mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE(-/-) mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R(-/-) ApoE(-/-) (BaffR.ApoE DKO) and BAFF-R(+/+)ApoE(-/-) (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulinsproduced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE(-/-) mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation.
What T-cell receptors can tell us about neurologic disease.
Source
From the Institute of Clinical Neuroimmunology, Ludwig Maximilians University of Munich, Munich, Germany.
Abstract
Chronic demyelinating polyradiculoneuropathy (CIDP) is an acquired, potentially crippling sensory-motor polyneuropathy of variable course.(1) It is likely autoimmune because sural nerve histopathology reveals infiltrating CD68+ macrophages, endoneurial and epineurial CD3+ T cells with immunoglobulin G, immunoglobulin M, and complement deposits on myelin sheaths.(1) Macrophages penetrate the basal lamina of Schwann cells and split myelin lamellae, a process referred to as "macrophage-mediated demyelination." Nerve injury ensues due to a combination of antibody-, complement-, and macrophage-dependent demyelination. The majority of patients therefore respond to corticosteroids, plasmapheresis, or IV immunoglobulin (IVIg). The Immune Globulin IV CIDP Efficacy (ICE) study, the largest therapeutic trial in CIDP, convincingly demonstrated short- and long-term benefits of IVIg treatment.(2) Response to plasmapheresis or IVIg is consistent with humoral and Fc receptor-mediated cellular effector mechanisms.
Cyclooxygenase-2-expressing macrophages in human pterygium co-express vascular endothelial growth factor.
Abstract
PURPOSE:
To evaluate cyclooxygenase-2 (COX-2) expression and to characterize COX-2-expressing stromal cells in human pterygium.
METHODS:
Primary pterygium tissue of Korean patients (eight males and nine females) was analyzed. The clinical characteristics were classified, and immunohistochemical staining using primary antibodies against cyclooxygenease-2, vascular endothelial growth factor-A, cluster of differentiation (CD)68, CD3, CD20, and leukocyte common antigen was performed.
RESULTS:
COX-2 expression was detected in all pterygium tissues evaluated (17 primary pterygia). Diffuse expression of COX-2 in the epithelial layer was observed in nine samples. Infiltration of strongly positive COX-2 cells into the epithelial layer was a more common observation than diffuse epithelial COX-2 expression. Scattered COX-2-expressing cells in the stromal layer were found in all samples. Some COX-2-positive cells were found within microvessels. In addition to stromal COX-2-expressing cells, a few vascular endothelial cells strongly expressed COX-2; however most of the vessels were negative for COX-2 expression. Stromal COX-2-expressing cells were positive for the macrophage marker CD68 and co-expressed vascular endothelial growth factor. COX-2 expression in normal conjunctiva was not observed in seven control samples.
CONCLUSIONS:
These COX-2- and vascular endothelial growth factor-expressing macrophages may have relevance to the pathogenesis of pterygium.
Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina.
Source
Department of Medicine, University of Ulsan, Seoul, Korea.
Abstract
ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases are emerging as key participants in the pathogenesis of vascular diseases. We studied the expression of ADAMTS-2, -3, -4 and -14 in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Tissue samples were gathered from 52 patients with AMI (n = 35) or stable angina (n = 17) who underwent directional coronary atherectomy. The specimens were stained with hematoxylin-eosin and analyzed immunohistochemically usingantibodies specific to ADAMTS-2, -3, -13 and -14, and markers for endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics of the groups were mostly similar. The proportion of smooth muscle α-actin-immunopositive area was smaller in the AMI group than in the stable angina group, but the areas immunopositive for CD31 or CD68 were higher in the AMI group. The relative areas immunopositive for ADAMTS-2, -3, and -13 in AMI were significantly larger than those in stable angina. However, the proportion of areas immunopositive for ADAMTS-14 did not differ between the two groups. Areas that stained for ADAMTS-2, -3, -13, and -14 largely overlapped with those positive for CD31 or CD68. The areas immunopositive for ADAMTS proteases were significantly correlated with CD31- or CD68-immunostained areas. In conclusions, ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. These results support a role for these enzymes in the pathogenesis of AMI.
High expression of tumor-infiltrating macrophages correlates with poor prognosis in patients with diffuse large B-cell lymphoma.
Source
State Key Laboratory of Oncology in Southern China, Department of Medical Oncology, Lymphoma Centre, Cancer Center of Sun Yat-sen University, 651 Dong Feng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.
Abstract
Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. Although the International Prognostic Index (IPI) provides a clinical model for risk stratification of patients with DLBCL, notable variability in outcome is still observed within the same IPI category. Tumor-infiltrating macrophages (also called Tumor-associated macrophages) are the major component in the microenvironment of DLBCL. Their correlation with the prognosis of DLBCL remains controversial. Using a CD68 antibody in immunohistochemical analysis, we studied the expression of CD68 in 112 Chinese patients with DLBCL, with 65 patients (58%) categorized as low CD68 expression and 47 patients (42%) as high CD68 expression. The complete response (CR) rate of patients with low CD68 expression was higher than that with high CD68 expression (66.1% vs. 51.6%), but there was no statistical significance (P = 0.060). The median survival time of patients with low CD68 expression was not achieved and that of high expression was 41 months (P = 0.029). The results suggest that higher expression of CD68 tended to yield poor treatment outcome of DLBCL.
Osteopontin induced by macrophages contribute to metachronous liver metastases in colorectal cancer.
Source
Ambulatory Treatment Center, Kinki University Hospital, Ohno-higashi Osaka-Sayama, Osaka, Japan.
Abstract
Even after radical surgery for stage II and stage III colorectal cancer, metachronous liver metastasis is frequently observed. The aim of this study was to identify the risk of metachronous liver metastasis with retrospective clinicopathological study. Immunohistochemistry was performed to evaluate the expression of Osteopontin (OPN), CD-68, and CD105 in 41 cases of stage II and stage III colorectal cancer tissue. Stage II and stage III colorectal cancer patients who had undergone R0 resection were classified into two groups: with metachronous liver metastasis (m-LM; n = 17) and without liver metastases (control; n = 24). Additionally, double-immunofluorescence staining was performed using antibodies to OPN and CD68. OPN-positive cells were frequently colocalized with CD68 immunoreactivity. OPN and microvascular density expression in the central area were significantly higher in the m-LM (OPN; control 4.3 ± 0.56, m-LV 10.8 ± 1.48, P < 0.05; microvascular density control 18.5 ± 2.86, m-LV 31.4 ± 4.39, P < 0.05), while CD68expression in the invasive margin was significantly higher in the control group (control 98.9 ± 7.31, m-LV 28.2 ± 3.18, P < 0.05). These results suggest that the risk of metachronous liver metastasis could be well predicted by immunohistochemical staining of OPN in the central areas, and CD68 in the invasive margins of tumors.
Photoletter to the editor: Generalized eruptive histiocytoma.
Source
Department of Dermatology, Andrology and S.T.Ds, 1st floor, Menoufiya University Hospital, Faculty of Medicine, Faculty of Medicine Street., Shibeen El Koom, 32817 Menoufiya Governorate, Egypt.
Abstract
Generalized eruptive histiocytoma is a rare form of non Langerhan's cell histiocytosis. The disease occurs mainly in adults and its etiology is still unknown. We describe a case of 48-year-old female with multiple, firm, hemispherical, redish brown papules. Lesions were distributed on the face, upper limbs and trunk. Patient's general examination and routine laboratory investigations were normal. Excisional biopsy was taken from one representative lesion. Histopathological examination revealed diffuse dermal histiocytic infiltration that was suggestive of generalized eruptive histiocytoma. Confirmatory immunohistochemical staining for CD68 antibody was done and revealed positive results. Based on clinical and histopathological criteria the diagnosis of generalized eruptive histiocytoma was established.In conclusion, we present a rare case of generalized eruptive histiocytoma which is an uncommon form of non Langerhan's cell histiocytosis. The disease does not require treatment since it is a self-healing disease.
Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
Source
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Diana.Lockwood@lshtm.ac.uk
Abstract
BACKGROUND:
Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions.
METHODOLOGY/PRINCIPAL FINDINGS:
TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68macrophage cell marker and S100.
CONCLUSIONS/SIGNIFICANCE:
Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.
Interleukin-6-producing dermoid cyst associated with multicentric Castleman's disease.
Source
Kobe Tokushukai Hospital, Kobe, Japan.
Abstract
Dysregulated overproduction of interleukin-6 (IL-6) from activated B cells in affected lymph nodes has been implicated in the pathogenesis of multicentric Castleman's disease (MCD), a rare lymphoproliferative disorder accompanied by systemic manifestations. We here report the case of a 32-year-old female presenting with MCD associated with a dermoid cyst in the pelvic cavity. The co-occurrence of MCD and dermoid cyst has not been reported before. Immunohistochemical analysis of the tissue sections showed IL-6 production in CD68-positive macrophage cells, which had infiltrated the dermoid cyst. Removal of the cyst resulted in partial improvement in systemic symptoms accompanied by a decrease in serum IL-6, while complete improvement was obtained by treatment with an anti-IL-6 receptor antibody following resection of the dermoid cyst. To the best of our knowledge, this is the first study to provide evidence of IL-6 production by CD68(+) cells in a dermoid cyst involved in MCD.
Expression of thymidine phosphorylase in lymph nodes involved with mycosis fungoides and sézary syndrome.
Source
Department of Pathology, Drexel University College of Medicine, 245 N. 15th Street, Mail Stop 435, Philadelphia, PA 19102, USA.
Abstract
Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation.
A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis.
Source
Departments of Clinical Neurosciences and Oncology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Abstract
Glioma cells in situ are surrounded by microglia, suggesting the potential of glioma-microglia interactions to produce various outcomes. As chemokines are important mediators of cell-cell communication, we sought first to identify commonly expressed chemokines in 16 human glioma lines. We found CCL2 (macrophage chemoattractant protein-1) messenger RNA to be expressed by the majority of glioma lines. However, these lines did not express the CCL2 receptor, CCR2, which was found on microglia. Next, we overexpressed CCL2 in the U87 glioma line, which has low basal level of CCL2, to investigate the hypothesis that glioma-secreted CCL2 interacts with microglia to affect glioma growth. Stable clones with 10- to 12-fold elevation of CCL2 have similar growth rate and invasive capacity as vector controls when cultured in isolation. However, in coculture with microglia in a three-dimensional collagen gel matrix, the invasiveness of CCL2-overexpressing clones was increased. Gene array analyses were then undertaken and they revealed that interleukin (IL)-6 was consistently increased in the coculture. Recombinant IL-6 enhanced the invasiveness of glioma cells when these were cultured alone, whereas a neutralizing antibody to IL-6 attenuated the microglia-stimulated glioma invasiveness. Finally, we found that human glioma specimens in situ contained IL-6 immunoreactivity that was expressed on CD68+ cells. This study has uncovered a mechanism by which glioma cells exploit microglia for increased invasiveness. Specifically, glioma-derived CCL2 acts upon CCR2-bearing microglia, which then produces IL-6 to stimulate gliomas. The CCL2/CCR2/IL-6 loop is a potential therapeutic target for the currently incurable malignant gliomas.
Neuroinflammation in Alzheimer's disease wanes with age.
Source
Department of Pathology, VU University Medical Center, P,O, Box 7057, 1007 MB Amsterdam, The Netherlands. jjm.hoozemans@vumc.nl.
Abstract
ABSTRACT:
BACKGROUND:
Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated.
METHODS:
In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodiesdirected against CD68 (KP1), HLA class II (CR3/43) and glial fibrillary acidic protein (GFAP).
RESULTS:
By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD.
CONCLUSION:
Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.
Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment.
Source
1Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Abstract
BACKGROUND:
Previous studies have demonstrated that angiotensin Type I receptor blockade (ARB) reduces proteinuria, reverses glomerular injury and glomerulosclerosis in rat models of diabetic nephropathy and glomerulonephritis. However, the cellular and molecular mechanisms are unclear. To investigate the role of cells of the bone marrow (BM) in glomerular repair seen during ARB administration, we induced progressive glomerulosclerosis in enhanced green fluorescent protein BM chimeric rats by a single injection of anti-Thy 1.1 monoclonal antibody, followed by unilateral nephrectomy.
METHODS:
Cohorts of rats received valsartan or no treatment from Week 2 to Week 8 after induction of disease. Renal function, urinary protein excretion and histological changes were examined 8 weeks after anti-Thy-1.1 monoclonalantibody injection.
RESULTS:
Valsartan administration improved renal function, reduced severity of glomerulosclrosis and markedly reduced mortality. Valsartan administration promoted regeneration of the glomerular tuft, lowered proteinuria and resulted in enhanced vascular endothelial growth factor (VEGF) expression in the cortex and glomerular tuft. In addition, valsartan promoted increased recruitment of BM-derived cells (BMDCs) many of which expressed VEGF and likely contributed directly to glomerular repair. Nearly all BMDCs recruited to the glomerulus expressed the monocyte/macrophage marker CD68.
CONCLUSIONS:
In conclusion, the data shows that ARB by valsartan prevents glomerulosclerosis progression by enhancing glomerular capillary repair which is associated with the recruitment of VEGF producing 'reparative' monocytes and macrophages from the BM.
Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.
Source
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Abstract
We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.
Comparative study of the in situ immune response in oral and nasal mucosal leishmaniasis.
Source
Laboratório de Imunoparasitologia, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
Abstract
Mucosal Leishmaniasis (ML) may occur in both nasal and oral mucosa. However, despite the impressive tissue destruction, little is known about the oral involvement. To compare some changes underlying inflammation in oral and nasal ML, we performed immunohistochemistry on mucosal tissue of 20 patients with ML (nasal [n = 12]; oral [n = 8] lesions) and 20 healthy donors using antibodies that recognize inflammatory markers (CD3, CD4, CD8, CD22, CD68, neutrophil elastase, CD1a, CLA, Ki67, Bcl-2, NOS2, CD62E, Fas and FasL). A significantly larger number of cells, mainly T cells and macrophages, were observed in lesions than in healthy tissue. In addition, high nitric oxide synthase 2 (NOS2) expression was associated with a reduced detection of parasites, highlighting the importance of NOS2 for parasite elimination. Oral lesions had higher numbers of neutrophils, parasites, proliferating cells and NOS2 than nasal lesions. These findings, together with the shorter duration of oral lesions and more intense symptoms, suggest a more recent inflammatory process. It could be explained by lesion-induced oral cavity changes that lead to eating difficulties and social stigma. In addition, the frequent poor tooth conservation and gingival inflammation tend to amplify tissue destruction and symptoms and may impair and confuse the correct diagnosis, thus delaying the onset of specific treatment.
© 2011 Blackwell Publishing Ltd.
Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma.
Source
Academic Oncology, University of Nottingham, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Abstract
The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8-30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of existing histological prognostic biomarkers. We note that a high macrophage count may be associated with neovascularisation and primary tumour growth, and may also promote invasion through lymphatic vessels.Modern Pathology advance online publication, 11 November 2011; doi:10.1038/modpathol.2011.182.
Immunoprecipitation of equine CD molecules using anti-human MABs previously analyzed by flow cytometry and immunohistochemistry.
Source
Institute for Zoo and Wildlife Research (IZW), Alfred Kowalke Str. 17, 10315 Berlin, Germany.
Abstract
Earlier studies investigating the cross-reactivity of antibodies submitted to the HLDA8 had used flow cytometry as a method of choice to screen mAbs for reactivity with equine leukocytes, including two-color flow-cytometry to characterize the lymphocyte population they detect. In addition, immuno-histochemistry (IHC) was used to detect distribution of positive cells in lymphoid tissue sections. In this study we performed immunoprecipitation (IP) to complement the previous results and add valuable information regarding the molecules detected by the cross-reactingantibodies. Surface molecules from primary equine PBMC or the equine cell line T8888 were biotinylated prior to precipitation to determine the molecular weight of the corresponding molecules in a western blot using streptavidin-AP. 21 out of 24mAbs precipitated the molecules with a MW corresponding to its human orthologue. Positive mAbs were directed against CD2, CD5, CD11a, CD11b, CD14, CD18, CD21, CD44, CD83, CD91, CD172a, MHCI and MHCII. Three mAbs directed against CD49d, CD163, and CD206 which were unambiguously identified earlier by flow cytometry failed to immunoprecipitate the corresponding CD molecule. MAbs detecting CD molecules which are expressed internally likeCD68 and mAbs of IgM class could not be included into this approach.
Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.
Comparison of E-selectin and the Other Inflammatory Markers in Lumbar Disc Herniation: A New Promising Therapeutical Window for Radicular Pain.
Source
Departments of *Neurosurgery †Pathology ‡Radiology, Baskent University, Ankara, Turkey.
Abstract
STUDY DESIGN:
Histopathologic and immunohistochemical analysis of the herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis.
OBJECTIVE:
The aim of this study was to investigate the prevalence of inflammatory cells in lumbar disc herniations (LDH) and compare the prevalence of leukocyte adhesion protein "E-selectin" with other inflammatory cells such as T cells, B cells, and macrophages.
SUMMARY OF BACKGROUND:
Studies on inflammatory cells and biochemical mediators of inflammation have suggested that these factors may play an important role in pathophysiology of radicular pain, and the medical therapy was formed against to block these cells and inflammatory cytokines.
METHODS:
The herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis were microscopically examined after staining with monoclonal antibodies of CD20, CD45, CD68, and E-selectin. Relative risk assessment of the straight-leg raising (SLR) test positivity or negativity with CD20, CD45, CD68, and E-selectin staining was investigated.
RESULTS:
Our data emphasize that, the cases with positive SLR test had higher rates of immunostaining with E-selectin and CD45. There were no statistically significant relationship between SLR positivity and CD20 and CD68.
CONCLUSIONS:
We suggest that E-selectin is as valuable as the other well-known inflammatory markers in the pathogenesis of LDH. In our opinion, beside the well-known nonsteroidal anti-inflammatory drugs, antagonists targeting E-selectin can be potentially effective therapeutics for controlling inflammation in LDH.
Histopathologic characterization of mild rejection (grade I) in skin biopsies of human hand allografts.
Source
Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria.
Abstract
Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty-seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA-1, ICAM-1, E-selectin, P-selectin, VE-cadherin, HLA-DR, IDO, and Foxp3). Expression was read with respect to time after transplant. The infiltrate was mainly comprised of CD3+T-lymphocytes. Among these, CD8+cells were more prominent than CD4+cells. CD20+B-lymphocytes were sparse and CD68+macrophages were found in some, but not all samples (approximately 10% of the infiltrate). The CD4/CD8-ratio was increased after the first year. C4d staining was mainly positive in samples at time-points later than 1 year. Adhesion molecules LFA-1, ICAM-1, E-selectin, P-selectin, and VE-cadherin were found upregulated, and for P-selectin, expression increased with time after transplant. IDO expression was strongest at 3 months-1 year post-transplant and a tendency toward more Foxp3+ cells at later time points was observed. Mild skin rejection after hand transplantation presents with a T-cell dominated dermal cell infiltrate and upregulation of adhesion molecules. The role of C4d expression after year one remains to be elucidated.
No comments:
Post a Comment