Detmers P A, Zhou D, Polizzi E, Thieringer R, Hanlon W A, Vaidya S, Bansal V
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021, USA.
J Immunol. 1998 Aug 15;161(4):1921-9.
Bacterial LPS elicits both rapid activation of the stress-activated MAP kinase p38 in polymorphonuclear leukocytes (PMN) and rapid adhesion of the PMN to ligands for the leukocyte integrin CD11b/CD18. The functional correlation between these two events was examined. The time course for tyrosine phosphorylation of p38 in PMN in response to 10 ng/ml LPS in 1% normal human serum was consistent with participation in signaling for leukocyte integrin-dependent adhesion, with transient phosphorylation peaking at 10 to 20 min. The concentration dependence of p38 phosphorylation also resembled that for PMN adhesion, with <1 ng/ml LPS eliciting a response. Phosphorylation was inhibited by mAb 60b against CD14, but not by mAb 26ic, a nonblocking anti-CD14. The function of p38 in integrin-dependent adhesion and the adhesion-dependent oxidative burst was tested using a specific inhibitor of p38, SB203580. SB203580 inhibited adhesion by diminishing the initial rate of adherence in response to both LPS and TNF, with a half-maximal concentration in the range of 0.1 to 0.6 microM. It did not, however, block adhesion in response to formyl peptide or PMA. The p38 inhibitor also blocked the adhesion-dependent oxidative burst with a half-maximal concentration similar to that for adhesion. Timed delivery of the compound during the lag phase preceding H2O2 production suggested that p38 kinase activity was required throughout the lag but not after the oxidase was assembled. These results suggest that p38 functions in PMN to signal leukocyte integrin-dependent adhesion and the subsequent massive production of reactive oxygen intermediates.
细菌脂多糖（LPS）可引发多形核白细胞（PMN）中应激激活的丝裂原活化蛋白激酶p38的快速激活，以及PMN与白细胞整合素CD11b/CD18配体的快速黏附。研究了这两个事件之间的功能相关性。在1%正常人血清中，PMN对10 ng/ml LPS反应时p38酪氨酸磷酸化的时间进程与参与白细胞整合素依赖性黏附的信号传导一致，短暂磷酸化在10至20分钟达到峰值。p38磷酸化的浓度依赖性也与PMN黏附相似，<1 ng/ml LPS即可引发反应。抗CD14单克隆抗体60b可抑制磷酸化，但非阻断性抗CD14单克隆抗体26ic则不能。使用p38的特异性抑制剂SB203580测试了p38在整合素依赖性黏附和黏附依赖性氧化爆发中的功能。SB203580通过降低对LPS和TNF反应时的初始黏附速率来抑制黏附，半数最大浓度在0.1至0.6 microM范围内。然而，它并不阻断对甲酰肽或佛波酯（PMA）的黏附。p38抑制剂也以与黏附相似的半数最大浓度阻断黏附依赖性氧化爆发。在H2O2产生之前的延迟期定时给予该化合物表明，在整个延迟期都需要p38激酶活性，但在氧化酶组装后则不需要。这些结果表明，p38在PMN中发挥作用，为白细胞整合素依赖性黏附和随后大量产生活性氧中间体提供信号。
