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101.
The immunologic privilege of the central nervous system (CNS) makes it crucial that CNS resident cells be capable of responding rapidly to infection. Astrocytes have been reported to express Toll-like receptors (TLRs), hallmark pattern recognition receptors of the innate immune system, and respond to their ligation with cytokine production. Astrocytes have also been reported to respond to cytokines of the adaptive immune system with the induction of antigen presentation functions. Here we have compared the ability of TLR stimuli and the adaptive immune cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to induce a variety of immunologic functions of astrocytes. We show that innate signals LPS- and poly I:C lead to stronger upregulation of TLRs and production of the cytokines IL-6 and TNF-alpha as well as innate immune effector molecules IFN-alpha4, IFN-beta, and iNOS compared with cytokine-stimulated astrocytes. Both innate stimulation and adaptive stimulation induce similar expression of the chemokines CCL2, CCL3, and CCL5, as well as similar enhancement of adhesion molecule ICAM-1 and VCAM-1 expression by astrocytes. Stimulation with adaptive immune cytokines, however, was unique in its ability to induce upregulation of MHC II and the functional ability of astrocytes to activate CD4(+) T cells. These results indicate potentially important and changing roles for astrocytes during the progression of CNS infection. 相似文献
102.
Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases 总被引:14,自引:0,他引:14
Yusuf-Makagiansar H Anderson ME Yakovleva TV Murray JS Siahaan TJ 《Medicinal research reviews》2002,22(2):146-167
This review focuses on providing insights into the structural basis and clinical relevance of LFA-1 and VLA-4 inhibition by peptides and small molecules as adhesion-based therapeutic strategies for inflammation and autoimmune diseases. Interactions of cell adhesion molecules (CAM) play central roles in mediating immune and inflammatory responses. Leukocyte function-associated antigen (LFA-1, alpha(L)beta(2), and CD11a/CD18) and very late antigen (VLA-4, alpha(4)beta(1), and CD49d/CD29) are members of integrin-type CAM that are predominantly involved in leukocyte trafficking and extravasation. LFA-1 is exclusively expressed on leukocytes and interacts with its ligands ICAM-1, -2, and -3 to promote a variety of homotypic and heterotypic cell adhesion events required for normal and pathologic functions of the immune systems. VLA-4 is expressed mainly on lymphocyte, monocytes, and eosinophils, but is not found on neutrophils. VLA-4 interacts with its ligands VCAM-1 and fibronectin (FN) CS1 during chronic inflammatory diseases, such as rheumatoid arthritis, asthma, psoriasis, transplant-rejection, and allergy. Blockade of LFA-1 and VLA-4 interactions with their ligands is a potential target for immunosuppression. LFA-1 and VLA-4 antagonists (antibodies, peptides, and small molecules) are being developed for controlling inflammation and autoimmune diseases. The therapeutic intervention of mostly mAb-based has been extensively studied. However, due to the challenging relative efficacy/safety ratio of mAb-based therapy application, especially in terms of systemic administration and immunogenic potential, strategic alternatives in the forms of peptide, peptide mimetic inhibitors, and small molecule non-peptide antagonists are being sought. Linear and cyclic peptides derived from the sequences of LFA-1, ICAM-1, ICAM-2, VCAM-1, and FN C1 have been shown to have inhibitory effects in vitro and in vivo. Finally, understanding the mechanism of LFA-1 and VLA-4 binding to their ligands has become a fundamental basis in developing therapeutic agents for inflammation and autoimmune diseases. 相似文献
103.
Slattery MJ Dong C 《International journal of cancer. Journal international du cancer》2003,106(5):713-722
We have studied human melanoma cell (C8161) adhesion and migration in response to stimulation by soluble collagen IV (CIV) using a modified Boyden chamber. In this modified chamber, shear flow can be introduced over the cell-substrate interface, affecting tumor cell chemotactic migration through a microporous filter. A relatively high level of intercellular adhesion molecule-1 (ICAM-1) was found on C8161 cells. In contrast, levels of beta(2)-integrins (e.g., LFA-1 and Mac-1), the molecules that would be necessary for C8161 stable adhesion to the endothelium substrate, were found to be very low on these melanoma cells. As a result, C8161 transendothelial migration under a flow condition of 4 dyn/cm(2) decreased by 70% as compared to static migration. When human neutrophils (PMNs) were present in the tumor cell suspension, C8161 migration recovered by 85% over C8161 cells alone under the 4 dyn/cm(2) flow condition. Blocking ICAM-1 on C8161 cells or Mac-1 on PMNs significantly inhibited C8161-PMN adhesion and subsequent C8161 migration through the endothelium under flow conditions. In addition, increased interleukin-8 production and Mac-1 expression by PMNs were detected when they were co-cultured with C8161 melanoma cells. These results suggest that transmigration of C8161 cells under flow conditions can be influenced by PMNs, mediated by Mac-1/ICAM-1 adhesive interactions and enhanced by altered cytokine production. 相似文献
104.
Pascal Bailly Eveliina Tontti Patricia Hermand Jean-Pierre Cartron Carl G. Gahmberg 《European journal of immunology》1995,25(12):3316-3320
Leukocyte adhesion involves the leukocyte-specific integrins CD11a/CD18, CD11b/CD18 and CD11c/CD18, which bind to intercellular adhesion molecules (ICAM). Three ICAM have been described, and are expressed on leukocytes and various other cells, but are absent from red cells. Here, we show that the red cell Landsteiner-Wiener (LW) blood group glycoprotein is an ICAM which binds to the leukocyte-specific integrins. This finding has important implications in red cell physiology. 相似文献
105.
Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration 总被引:10,自引:0,他引:10 下载免费PDF全文
Penfold PL Wen L Madigan MC Gillies MC King NJ Provis JM 《Clinical and experimental immunology》2000,121(3):458-465
Whilst animal studies and a pilot clinical trial suggest that intravitreal triamcinolone acetonide (TA) may be useful in the treatment of age-related macular degeneration (AMD), its mode of action remains to be fully elucidated. The present study has investigated the capacity of TA to modulate the expression of adhesion molecules and permeability using a human epithelial cell line (ECV304) as a model of the outer blood-retinal barrier (BRB). The influence of TA on the expression of ICAM-1 and MHC-I was studied on resting and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and/or tumour necrosis factor-alpha (TNF-alpha)-activated cells using flow cytometry and immunocytochemistry. Additionally, ECV304 cells were grown to confluence in uncoated Transwell chambers; transepithelial resistance (TER) across resting and PMA-activated cells was monitored. TA significantly decreased the paracellular permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent with immunocytochemical observations. PMA-induced permeability changes were dose-dependent and TA decreased permeability of both resting and PMA-activated monolayers. MHC-I expression by ECV304 cells however, was not significantly affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro correlate with clinical observations, suggesting re-establishment of the BRB and down-regulation of inflammatory markers are the principal effects of intravitreal TA in vivo. The results further indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae. 相似文献
106.
107.
Haritopoulos KN Lazaris AC Kavantzas N Tseleni-Balafouta S Thomopoulou G Aroni K 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(3):421-429
Malignant melanoma usually progresses from the intraepidermal microenvironment through a distinct radial growth phase, in which malignant potential cannot always be accurately evaluated, to invasion of the dermis (vertical growth phase) and metastasis. During these stages malignant cells interact with each other and with the extracellular matrix. This interaction is mediated by cell surface adhesion molecules such as the beta(3) integrin subunit and ICAM-1. Our aim was to investigate whether the expression of these two molecules is associated with the various histopathologic prognosticators commonly evaluated in malignant melanoma. Using a standard three-step immunoperoxidase technique we evaluated the above molecules' expression in a documented series of 66 cutaneous malignant melanomas. Forty-five were superficial spreading melanomas, including 18 in mixed growth phase. Positive immunoreaction was estimated by image analysis. ICAM-1 immunopositivity status was significantly more frequent among malignant melanomas of the nodular type (p=0.0001), and was associated with the vertical growth phase, Breslow thickness of >0.77 mm, and with evident lymphocytic infiltration. beta(3) integrin immunopositivity showed similar results in certain respects; it was more frequently detected in superficial spreading melanomas in which vertical growth had developed (p=0.002) and in cases with regression. There appears to be an association of these molecules with histopathologic features that predict increased tumorigenicity of malignant melanocytes. 相似文献
108.
109.
目的 研究共刺激途径B7/CD28 和ICAM1/LFA1 对T 细胞活化以及B 细胞效应的作用。方法 在体外建立APCTB 细胞反应系统, 用B71 单抗和ICAM1 单抗分别阻断B7/CD28 和ICAM1/LFA1 共刺激途径, 利用3 HTdR 法检测T 细胞增殖,ELISA 法测定B 细胞分泌的抗体, 用RTPCR 法检测细胞因子基因的表达。结果 B71 单抗和ICAM1 单抗均可抑制T 细胞增殖及IL2 的产生。B71 单抗可下调B 细胞抗体的产生( P< 0 .05) , 而ICAM1 单抗未见明显的抑制( P> 0 .05) 。B71 单抗和CsA 联用能阻断T 细胞增殖活性及B 细胞的效应, 而ICAM1 单抗和CsA联用则无此作用。B71 单抗能下调IL2 和IFNγm RNA 表达,B71 单抗和CsA 联用则阻断IL2 和IFNγm RNA 表达,IL4 和IL10 m RNA 仍可表达。结论 B7/CD28 和ICAM1/LFA1 共刺激途径在T 细胞活化中具有不同的作用,B71 单抗和CsA 联用可导致T 细胞功能失活即无能。 相似文献
110.
为了观察血管紧张素II (AII)对人单核细胞株THP 1分泌单核细胞趋化因子 (MCP 1)、人类脐静脉内皮细胞(HUVEC )分泌细胞间粘附分子 (ICAM 1)的影响及AII对HUVEC与THP 1的粘附功能的影响 ,我们利用ELISA法检测AII作用后THP 1分泌MCP 1及HUVEC分泌ICAM 1的表达 ,利用计数法观察经AII作用的HUVEC与THP 1的粘附率。结果发现四种不同浓度的AII(10 6、 10 7、 10 8、 10 9mol/L )刺激THP 1及HUVEC 2 4h后 ,MCP 1及ICAM 1的分泌明显增加 ,AII(10 6mol/L )作用HUVEC 6h后 ,其对THP 1细胞粘附率明显增加 ,表明AII具有调节THP 1分泌MCP 1及HUVEC分泌ICAM 1的作用 ,AII可通过致炎症作用参与动脉粥样硬化的发病过程。 相似文献