Role of macrophage inflammatory protein 2 in acute lung injury in murine peritonitis.
BACKGROUND
Acute lung injury is a frequent extraabdominal complication of bacterial peritonitis, and neutrophil plays an important role in this lung damage. Macrophage inflammatory protein 2 (MIP-2) serves the same chemotactic function as IL-8 which is a potent neutrophil chemotactic factor in humans, and we investigated the role of MIP-2 associated with neutrophil recruitment in the lung of murine peritonitis.


METHODS
Cecal ligation and puncture (CLP) were performed on mice. MIP-2 levels in blood and lung tissue, MIP-2 mRNA expression in lung tissue and bronchoalveolar lavage fluid (BALF), and CD11b expression on peripheral blood neutrophil and BALF cells were determined after CLP. In addition, we investigated the effect of anti-MIP-2 antibody on the lung injury associated with peritonitis.


RESULTS
MIP-2 mRNA expression was observed in lung tissue after CLP and numerous neutrophils were accumulated in the lung under those conditions. Anti-MIP-2 antibody contributed to the inhibition of the CD11b expression and chemotaxis of pulmonary neutrophils, lung edema, and thus the reduction in peritonitis-related mortality.


CONCLUSIONS
MIP-2 plays a pivotal role in neutrophil recruitment in the lung following peritonitis, and control of neutrophil accumulation in the lung by neutralizing MIP-2 is recommended as a new therapeutic approach to the lung damage associated with peritonitis.
Tsujimoto
Hironori
H
Department of Surgery I, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Ono
Satoshi
S
Mochizuki
Hidetaka
H
Aosasa
Suefumi
S
Majima
Takashi
T
Ueno
Chikara
C
Matsumoto
Atsushi
A
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology; D010538:Peritonitis / Q000150:complications / Q000276:immunology* / Q000401:mortality; D011654:Pulmonary Edema / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000150:complications / Q000276:immunology / Q000401:mortality; D015996:Survival Rate
D000906:Antibodies; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger