Role of β1 integrin in tissue homing of neutrophils during sepsis.
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.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA. sarangipp@mail.nih.gov
Pranita P
PP
Sarangi
Young-Min
YM
Hyun
Yelena V
YV
Lerman
Anthony P
AP
Pietropaoli
Minsoo
M
Kim
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology; D018821:CD18 Antigens / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000209:etiology; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D018805:Sepsis / Q000209:etiology*; D015854:Up-Regulation
D000890:Anti-Infective Agents; D018821:CD18 Antigens; D019012:Integrin beta1; D008070:Lipopolysaccharides; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid