Yurochko A D, Liu D Y, Eierman D, Haskill S
University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7295.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9034-8. doi: 10.1073/pnas.89.19.9034.
Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common beta chain of the beta 1 subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1 beta, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common beta chain of the beta 2 family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the alpha chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2 fragment and the whole IgG molecule could. Interleukin 1 beta secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.
整合素是在单核细胞上发现的细胞表面受体，可促进与细胞和细胞外基质的黏附。这些整合素被认为参与了单核细胞黏附于各种细胞外基质后观察到的选择性基因诱导过程。为了研究这一假设，我们用针对不同整合素受体的单克隆抗体刺激单核细胞，以特异性模拟整合素受体-配体相互作用。整合素β1亚家族的共同β链的结合导致炎症介质基因白细胞介素1β、白细胞介素1受体拮抗剂和单核细胞黏附衍生炎症基因6（MAD-6）的表达，而β2家族的共同β链的结合则不会。此外，为了表征整合素介导的基因诱导，我们检测了针对整合素受体α链的抗体调节基因表达的能力。极迟抗原4（VLA-4）受体的结合导致所有介质基因的诱导。需要受体交联，因为单个Fab片段无法刺激基因诱导，而二价F(ab')2片段和完整的IgG分子可以。白细胞介素1β的分泌取决于所使用的抗整合素抗体。一些抗体需要第二个信号，而对于其他抗体，直接结合就足以产生蛋白质。总之，整合素受体的结合调节了炎症介质mRNA和蛋白质的产生。这些结果表明，整合素依赖性识别和黏附可能为单核细胞渗出过程中炎症反应的启动提供关键信号。
