Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion

We evaluated the roles of the C-X-C chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) as wel l as the complement activation product C5a in development of lung injury af ter hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b and CD 18, but not CD11a, were upregulated on neutrophils [bronchoalveolar lavage (BAL) and blood] and lung macrophages. BAL levels of CINC and MIP-2 were in creased during the ischemic and reperfusion periods. Treatment with either anti-CINC or anti-MIP-2 IgG significantly reduced lung vascular permeabilit y and decreased lung myeloperoxidase content by 93 and 68%, respectively (P < 0.05). During the same period, there were significant increases in serum C5a-related neutrophil chemotactic activity. Treatment with anti-C5a decre ased lung vascular permeability, lung myeloperoxidase, and BAL CINC by 51, 58, and 23%, respectively (P < 0.05). The data suggest that the C-X-C chemo kines CINC and MIP-2 as well as the complement activation product C5a are r equired for lung neutrophil recruitment and full induction of lung injury a fter hindlimb ischemia-reperfusion in rats.