Eotaxin/CCL11 is a negative regulator of neutrophil recruitment in a murine model of endotoxemia.
Eotaxin/CCL11 is a chemokine that has been primarily characterized with respect to its eosinophil chemoattractant activity. However, the broad tissue expression of eotaxin/CCL11 suggests that it may have other unknown activities. We have used a murine model of endotoxemia to study the role of eotaxin/CCL11 in neutrophil recruitment. We demonstrate that eotaxin/CCL11 is acutely upregulated in the serum, peritoneal wash, and lungs of mice given an intraperitoneal lipopolysaccharide (LPS) challenge. Furthermore, immunoneutralization of eotaxin/CCL11 in this model results in a significant increase in the number of neutrophils within the lung after LPS challenge. When eotaxin/CCL11 knockout mice were challenged with LPS, these mice had increased peritoneal neutrophils, but not lung neutrophils, compared to the wild-type controls. Administration of eotaxin/CCL11 to eotaxin(-/-) mice suppressed endotoxemia-associated peritoneal neutrophils. The presence or absence of eotaxin/CCL11 did not affect the number of peritoneal macrophages in these mice. These data indicate that eotaxin/CCL11 plays a novel regulatory role during the acute inflammatory response and suggest that constitutive expression of this chemokine within tissues such as the gut, lung, heart, and placenta might be important in downregulating acute inflammatory processes within these tissues.
Cheng
Sara S
SS
Graduate Program in Cellular and Molecular Biology, University of Michigan Medical Center, Ann Arbor 48109, USA.
Lukacs
Nicholas W
NW
Kunkel
Steven L
SL
D000818:Animals; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D018925:Chemokines / Q000037:antagonists & inhibitors; D019742:Chemokines, CC / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D019446:Endotoxemia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000037:antagonists & inhibitors; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism
C515457:Ccl11 protein, mouse; C515451:Ccl7 protein, mouse; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018945:Monocyte Chemoattractant Proteins; C070959:Ccl6 protein, mouse; D009195:Peroxidase