MONOCYTE-ENDOTHELIAL ADHESION IN CHRONIC RHEUMATOID-ARTHRITIS - INSITU DETECTION OF SELECTIN AND INTEGRIN-DEPENDENT INTERACTIONS
MONOCYTE-ENDOTHELIAL ADHESION IN CHRONIC RHEUMATOID-ARTHRITIS - INSITU DETECTION OF SELECTIN AND INTEGRIN-DEPENDENT INTERACTIONS
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DOI：
10.1172/jci116500
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发表时间：
1993-06-01
影响因子：
15.9
通讯作者：
STOOLMAN, LM
中科院分区：
文献类型：
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作者：
GROBER, JS;BOWEN, BL;STOOLMAN, LM
血液单核细胞是类风湿性滑膜炎组织巨噬细胞的主要储存库。受体介导的循环细胞和滑膜小静脉之间的粘附相互作用启动募集。这些相互作用主要在培养的内皮细胞中进行了研究。因此，特异性粘附受体的功能活性，如内皮选择素和白细胞整合素，还没有直接在患病组织中进行评估。因此，我们研究了单核细胞微血管的相互作用，类风湿性滑膜炎修改斯坦珀-伍德拉夫冷冻切片结合试验最初开发的研究淋巴细胞归巢。低至5 × 10（5）个细胞/ml的浓度下，单核细胞与低或高内皮内衬的微静脉发生特异性结合。P-选择素特异性mAb（CD 62，GMP-140 / PADGEM）在所有检查的滑膜炎标本中阻断粘附> 90%。相反，在正常包皮和胎盘的冰冻切片中，P-选择素介导的粘附到微血管的能力较低或不存在。E-选择素（ELAM-1）特异性单克隆抗体阻断20-50%的单核细胞附着在一些RA滑膜标本，但在其他人没有效果。对LFA-1、Mo 1/Mac 1、整合素β 2链和L-选择素特异的mAb分别抑制30-40%的粘附。整合素β 1链特异性单克隆抗体抑制淘析单核细胞的附着高达20%。我们的结论是，P-选择素与滑膜微血管系统启动抗剪切粘附单核细胞在斯坦珀-伍德拉夫测定和稳定债券形成的其他选择素和整合素。因此，冷冻切片结合试验允许直接评价炎症组织中白细胞-微血管粘附相互作用，并表明P-选择素在体内单核细胞募集中的重要作用。
Blood monocytes are the principal reservoir for tissue macrophages in rheumatoid synovitis. Receptor-mediated adhesive interactions between circulating cells and the synovial venules initiate recruitment. These interactions have been studied primarily in cultured endothelial cells. Thus the functional activities of specific adhesion receptors, such as the endothelial selectins and the leukocytic integrins, have not been evaluated directly in diseased tissues. We therefore examined monocyte-microvascular interactions in rheumatoid synovitis by modifying the Stamper-Woodruff frozen section binding assay initially developed to study lymphocyte homing. Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 X 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140 / PADGEM) blocked adhesion by > 90% in all synovitis specimens examined. In contrast, P-selectin-mediated adhesion to the microvasculature was either lower or absent in frozen sections of normal foreskin and placenta. mAbs specific for E-selectin (ELAM-1) blocked 20-50% of monocyte attachment in several RA synovial specimens but had no effect in others. mAbs specific for LFA-1, Mo1/Mac 1, the integrin beta2-chain, and L-selectin individually inhibited 30-40% of adhesion. An mAb specific for the integrin beta1-chain inhibited the attachment of elutriated monocytes up to 20%. We conclude that P-selectin associated with the synovial microvasculature initiates shear-resistant adhesion of monocytes in the Stamper-Woodruff assay and stabilizes bonds formed by other selectins and the integrins. Thus the frozen section binding assay permits direct evaluation of leukocyte-microvascular adhesive interactions in inflamed tissues and suggests a prominent role for P-selectin in monocyte recruitment in vivo.