Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA.
Shock. 2012 Aug;38(3):281-7. doi: 10.1097/SHK.0b013e31826136f8.
Aberrant activation of neutrophils during sepsis results in the widespread release of proinflammatory mediators, leading to multiorgan system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multiorgan system failure and death. One of the pivotal components of neutrophil migration during inflammation is the expression of surface integrins. In this study, we show that administration of a cyclic analog of RGD peptide (Arg-Gly-Asp) significantly reduced the number of tissue-invading neutrophils and the degree of sepsis-induced lethality in mice as compared with control peptide. Second, β1 integrin (CD29) was highly upregulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of β1 integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of β1 integrin is important for modulating neutrophil trafficking during sepsis and that therapeutics designed against β1 integrins may be beneficial.
在脓毒症中，中性粒细胞的异常激活导致促炎介质的广泛释放，从而导致多器官系统衰竭和死亡。然而，在脓毒症中，中性粒细胞的异常激活导致有害炎症介质的广泛释放，导致宿主组织损伤，从而导致多器官系统衰竭和死亡。中性粒细胞在炎症过程中的迁移的关键组成部分之一是表面整合素的表达。在这项研究中，我们表明，与对照肽相比，施用 RGD 肽（精氨酸-甘氨酸-天冬氨酸）的环状类似物可显着减少组织浸润的中性粒细胞数量和脓毒症诱导的致死率。其次，β1 整合素（CD29）在脓毒症患者和动物分离的中性粒细胞中高度上调。最后，从粒细胞中条件性遗传消融β1 整合素也改善了脓毒症动物的存活和细菌清除率。因此，我们的结果表明，β1 整合素的表达对于调节脓毒症期间中性粒细胞的迁移很重要，并且针对β1 整合素的治疗可能是有益的。
