Haskard D, Cavender D, Beatty P, Springer T, Ziff M
J Immunol. 1986 Nov 1;137(9):2901-6.
Adhesion of lymphocytes to vascular endothelium is the first event in the passage of lymphocytes into a chronic inflammatory reaction. To investigate molecular mechanisms of T-EC adhesion, monoclonal antibodies (Mab) against T cell surface antigens have been tested for inhibition of binding. Baseline and phorbol ester-stimulated adhesion were strongly inhibited by either Mab 60.3 (reactive with the beta-chain of the LFA-1, OKM1, and p150,95 molecules) or by Mab TS 1/22 (specific for the alpha-chain of LFA-1). Although the increased binding of phorbol ester-stimulated lymphocytes was inhibited by anti-LFA-1 antibody, there was no increased expression of LFA-1 on phorbol ester-stimulated T cells, as determined by FACS analysis. Maximal inhibition of unstimulated and phorbol ester-stimulated T-EC adhesion was seen at Mab concentrations of 1 microgram/ml. In contrast, LPS- and IL 1-enhanced T-EC adhesion were only weakly inhibited by these antibodies. Mab 60.3 and TS 1/22 did not stain either unstimulated EC or LPS- or IL 1-stimulated EC, as measured by FACS analysis; moreover, preincubation of EC alone with these antibodies did not lead to inhibition of T-EC binding. Adhesion was not affected by Mab against the sheep erythrocyte receptor (LFA-2), a nonpolymorphic HLA class 1 framework antigen, or against LFA-3, the alpha-chain of OKM1, or the alpha-chain of p150,95. These results suggest that the mechanism of binding of lymphocytes to unstimulated endothelium differs from that to stimulated endothelium. LFA-1 appears to be an important adhesion-related molecule for binding to unstimulated endothelium. However, the increased lymphocyte adhesion to IL 1- or LPS-stimulated EC observed in these experiments appears to be relatively independent of LFA-1. The increased adhesion to stimulated EC could be due either to an increase in the avidity or the density of the EC receptor molecules ordinarily involved in unstimulated T-EC binding or to the formation of alternative receptors on the stimulated EC that are not present on unstimulated cells.
淋巴细胞与血管内皮的黏附是淋巴细胞进入慢性炎症反应过程中的首个事件。为了研究T细胞与内皮细胞（T-EC）黏附的分子机制，已对针对T细胞表面抗原的单克隆抗体（Mab）进行了结合抑制试验。Mab 60.3（与淋巴细胞功能相关抗原-1（LFA-1）的β链、OKM1和p150,95分子反应）或Mab TS 1/22（对LFA-1的α链具有特异性）可强烈抑制基础状态及佛波酯刺激后的黏附。尽管抗LFA-1抗体可抑制佛波酯刺激的淋巴细胞结合增加，但通过荧光激活细胞分选术（FACS）分析确定，佛波酯刺激的T细胞上LFA-1的表达并未增加。在Mab浓度为1微克/毫升时，未刺激及佛波酯刺激的T-EC黏附受到最大程度的抑制。相比之下，脂多糖（LPS）和白细胞介素1（IL 1）增强的T-EC黏附仅受到这些抗体的微弱抑制。通过FACS分析测量，Mab 60.3和TS 1/22既不标记未刺激的内皮细胞，也不标记LPS或IL 1刺激的内皮细胞；此外，仅将内皮细胞与这些抗体预孵育不会导致T-EC结合受到抑制。黏附不受针对绵羊红细胞受体（LFA-2，一种非多态性的人类白细胞抗原（HLA）I类框架抗原）、LFA-3、OKM1的α链或p150,95的α链的Mab的影响。这些结果表明，淋巴细胞与未刺激内皮细胞的结合机制不同于与刺激内皮细胞的结合机制。LFA-1似乎是与未刺激内皮细胞结合的重要黏附相关分子。然而，在这些实验中观察到的淋巴细胞与IL 1或LPS刺激的内皮细胞黏附增加似乎相对独立于LFA-1。与刺激内皮细胞黏附增加可能是由于通常参与未刺激T-EC结合的内皮细胞受体分子的亲和力或密度增加，或者是由于刺激内皮细胞上形成了未刺激细胞上不存在的替代受体。
