Lundberg C, Wright S D
Department of Inflammation Research, Pharmacia AB, Uppsala, Sweden.
Blood. 1990 Sep 15;76(6):1240-5.
Adherence of leukocytes to the endothelium is a prerequisite for infiltration and accumulation of cells at an inflammatory site. Recent studies suggest that the CD11/CD18 family of adhesion-promoting receptors plays a crucial role in the initial adherence of polymorphonuclear leukocytes (PMNs) to endothelium. We have studied the effect of the anti-CD18 monoclonal antibody (MoAb) IB4, on movement of PMN in rabbits. Accumulation of PMNs in the skin induced by a local injection of the chemoattractant, zymosan-activated serum (ZAS), was strongly inhibited, in a dose-dependent fashion, by intravenous injection of IB4. A greater than 95% reduction in PMN accumulation was seen with 1 mg IB4/kg body weight, the highest dose used. PMN-dependent plasma leakage in the ZAS-injected skin sites was also inhibited by pretreatment with MoAb IB4, with a similar dose dependence. Histamine-induced plasma leakage, which is PMN independent, was not affected by this treatment. F(ab)2 fragments of IB4 were as effective as the whole immunoglobulin G molecule in reducing PMN accumulation. The half-life of circulating IB4 in rabbits was found to be 11.5 hours. These results are consistent with in vitro studies that show that binding of PMNs to endothelium requires both expression of CD11/CD18 molecules and activation of the PMNs by agonists, and confirm that sites on CD11/CD18 that recognize endothelial cells are blocked by IB4. Other investigators have shown that injection of chemoattractants into the blood stream causes a rapid neutropenia associated with accumulation of PMNs in the lung. We find that intravenous treatment of animals with IB4 did not block the transient accumulation of PMNs in the lung induced by formyl-methionyl-leucyl-phenylalanine, suggesting that this accumulation occurs by a mechanism that does not require CD11/CD18 molecules.
白细胞与内皮细胞的黏附是细胞在炎症部位浸润和聚集的前提条件。最近的研究表明，促进黏附的CD11/CD18受体家族在多形核白细胞（PMN）与内皮细胞的初始黏附中起关键作用。我们研究了抗CD18单克隆抗体（MoAb）IB4对兔PMN运动的影响。静脉注射IB4以剂量依赖的方式强烈抑制了局部注射趋化剂酵母聚糖激活血清（ZAS）诱导的皮肤中PMN的聚集。使用的最高剂量为1 mg IB4/kg体重时，PMN聚集减少了95%以上。MoAb IB4预处理也抑制了ZAS注射皮肤部位PMN依赖性血浆渗漏，且具有相似的剂量依赖性。组胺诱导的血浆渗漏不依赖于PMN，不受该处理的影响。IB4的F(ab)2片段在减少PMN聚集方面与完整的免疫球蛋白G分子一样有效。发现兔体内循环的IB4半衰期为11.5小时。这些结果与体外研究一致，体外研究表明PMN与内皮细胞的结合既需要CD11/CD18分子的表达，也需要激动剂对PMN的激活，并证实识别内皮细胞的CD11/CD18位点被IB4阻断。其他研究人员表明，向血流中注射趋化剂会导致快速中性粒细胞减少，伴有PMN在肺中的聚集。我们发现用IB4对动物进行静脉治疗并不能阻断甲酰甲硫氨酰亮氨酰苯丙氨酸诱导的PMN在肺中的短暂聚集，这表明这种聚集是通过一种不需要CD11/CD18分子的机制发生的。
