Blocking neutrophil integrin activation prevents ischemia–reperfusion injury

• DOI: 10.1084/jem.20142358
• Publication Date: 2015-07-14T02:04:42Z
• Authors: Tadayuki Yago; Brian G. Petrich; Nan Zhang; Zhenghui Liu; Bojing Shao; Mark H. Ginsberg; Rodger P. McEver
• Keywords: Talin; Kidney Disease; Neutrophils; Immunology; Blotting, Western; Mutation, Missense; Mice, Transgenic; 612; Medical and Health Sciences; Transgenic; Article; Mice; Cell Movement; 616; 2.1 Biological and endogenous factors; Animals; Immunoprecipitation; Leukocyte Rolling; Aetiology; DNA Primers; Blotting; 3. Good health; CD18 Antigens; Reperfusion Injury; Mutation; Kidney Diseases; Missense; Western

Neutrophil recruitment, mediated by β2 integrins, combats pyogenic infections but also plays a key role in ischemia–reperfusion injury and other inflammatory disorders. Talin induces allosteric rearrangements integrins that increase affinity for ligands (activation). links to actin proteins enable formation of adhesions. Structural studies have identified talin1 mutant (L325R) perturbs activation without impairing talin’s capacity link proteins. Here, we found mice engineered express only talin1(L325R) myeloid cells were protected from renal injury. Dissection neutrophil function vitro vivo revealed neutrophils had markedly impaired chemokine-induced, integrin–mediated arrest, spreading, migration. Surprisingly, exhibited normal selectin-induced, slow rolling, sharp contrast the defective rolling lacking or expressing (W359A) blocks talin interaction with integrins. These reveal importance talin-mediated They further show arrest requires recruitment However, although integrin is dispensable.