Neutrophil sequestration in liver and lung is differentially regulated by C-X-C chemokines during experimental peritonitis.
C-X-C chemokines play an important role in the migration and activation of neutrophils (PMNs) during an inflammatory event. We measured mRNA and protein expression of the murine C-X-C chemokines macrophage inflammatory protein-2 (MIP-2) and KC in the lungs, liver, blood, and peritoneal cavity of Swiss Webster mice after cecal ligation and puncture (CLP). Neutralizing antibodies to MIP-2 and KC were also used to determine the biological effects of these chemokines on neutrophil sequestration and organ injury in the CLP model. The data showed that early after CLP, MIP-2 mRNA and protein were expressed predominantly by the lung, whereas KC mRNA and protein were expressed by the liver. Inhibition of MIP-2 reduced both lung neutrophil sequestration and peritoneal neutrophil migration. Inhibition of KC had no effect on overall neutrophil sequestration in liver but reduced injury as measured by serum transaminases. An early survival benefit was found with anti-KC treatment, although overall survival was not different. Our study showed a differential expression by organs of C-X-C chemokines during sepsis and suggested that such chemokine effects are tissue-specific.
Mercer-Jones
M A
MA
Veterans Affairs Medical Center, University of Louisville School of Medicine, Kentucky 40292, USA.
Shrotri
M S
MS
Peyton
J C
JC
Remick
D G
DG
Cheadle
W G
WG
D000818:Animals; D002432:Cecum / Q000502:physiology; D002465:Cell Movement / Q000276:immunology*; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC / Q000502:physiology*; D002630:Chemotactic Factors / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D008026:Ligation; D008297:Male; D051379:Mice; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology; D011677:Punctures
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D007106:Immune Sera; D015846:Monokines; C074302:keratinocyte-derived chemokines