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 well as the complement activation product C5a in development of lung injury after hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b and CD18, but not CD11a, were upregulated on neutrophils [bronchoalveolar lavage (BAL) and blood] and lung macrophages. BAL levels of CINC and MIP-2 were increased during the ischemic and reperfusion periods. Treatment with either anti-CINC or anti-MIP-2 IgG significantly reduced lung vascular permeability 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 decreased 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 chemokines CINC and MIP-2 as well as the complement activation product C5a are required for lung neutrophil recruitment and full induction of lung injury after hindlimb ischemia-reperfusion in rats.
Bless
N M
NM
Department of Trauma Surgery, University of Freiburg, D-79106 Freiburg, Germany.
Warner
R L
RL
Padgaonkar
V A
VA
Lentsch
A B
AB
Czermak
B J
BJ
Schmal
H
H
Friedl
H P
HP
Ward
P A
PA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054426:Chemokine CXCL2; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000276:immunology; D015936:Complement C5a / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D006133:Growth Substances / Q000032:analysis / Q000276:immunology; D006614:Hindlimb / Q000098:blood supply*; D036341:Intercellular Signaling Peptides and Proteins; D007511:Ischemia / Q000097:blood / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D015846:Monokines / Q000032:analysis / Q000276:immunology; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*
D000906:Antibodies; D015815:Cell Adhesion Molecules; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D015936:Complement C5a