Kubes P, Niu X F, Smith C W, Kehrli M E, Reinhardt P H, Woodman R C
Immunology Research Group, University of Calgary, Alberta, Canada.
FASEB J. 1995 Aug;9(11):1103-11.
It is generally accepted that the beta 2-integrin is restricted to mononuclear leukocytes. The objective of this study was to determine whether neutrophils can also express beta 1-integrin (specifically alpha 4 beta 1) and whether this can support neutrophil adhesion to endothelial cells and to extracellular matrix. We stimulated neutrophils with dihydrocytochalasin B (DHCB) and various chemotactic stimuli and observed that chemotactic stimuli induced neutrophil adhesion via beta 2-integrin (CD18), whereas DHCB and either fMLP, PAF, or IL-8 induced adhesion to endothelium or protein-coated plastic that was not inhibitable by anti-CD18 antibody. beta 2-integrin-deficient cells, which did not respond to chemotactic stimuli alone, also adhered avidly in the presence of chemotactic stimuli and DHCB. The induced neutrophil adhesion was inhibited by antibody to beta 1- or alpha 4-integrin chains, but only if an anti-beta 2-integrin antibody was also present. Flow cytometry revealed increased expression of both beta 1 and alpha 4 in the presence of fMLP plus DHCB. Transendothelial migration of neutrophils induced by chemotactic stimuli alone also increased expression of beta 1 and alpha 4. Transmigration across deendothelialized membranes induced a similar beta 1 expression on neutrophils suggesting that events other than an endothelial signal elicited beta 1-integrin expression. Transmigration-induced beta 1-dependent expression translated into only modest adhesion to protein-coated plastic. These data suggest that both a pharmacological (DHCB) and a physiological (transmigration) stimulus can invoke expression of alpha 4 and beta 1 on human neutrophils to mediate adhesion.
一般认为β2整合素仅限于单核白细胞。本研究的目的是确定中性粒细胞是否也能表达β1整合素（特别是α4β1），以及这是否能支持中性粒细胞与内皮细胞和细胞外基质的黏附。我们用二氢细胞松弛素B（DHCB）和各种趋化刺激物刺激中性粒细胞，观察到趋化刺激物通过β2整合素（CD18）诱导中性粒细胞黏附，而DHCB与fMLP、PAF或IL-8一起诱导对内皮或蛋白包被塑料的黏附，这种黏附不能被抗CD18抗体抑制。单独对趋化刺激物无反应的β2整合素缺陷细胞，在存在趋化刺激物和DHCB的情况下也能强烈黏附。诱导的中性粒细胞黏附被抗β1或α4整合素链的抗体抑制，但前提是也存在抗β2整合素抗体。流式细胞术显示在fMLP加DHCB存在的情况下，β1和α4的表达均增加。仅由趋化刺激物诱导的中性粒细胞跨内皮迁移也增加了β1和α4的表达。跨去内皮化膜的迁移在中性粒细胞上诱导了类似的β1表达，这表明除了内皮信号之外的其他事件引发了β1整合素的表达。迁移诱导的β1依赖性表达仅转化为对蛋白包被塑料的适度黏附。这些数据表明，药理学（DHCB）和生理学（迁移）刺激均可引发人中性粒细胞上α4和β1的表达以介导黏附。
