Long-term impaired neutrophil migration in mice overexpressing human interleukin-8.
The proinflammatory chemokine interleukin-8 (IL-8/NAP-1) has been implicated in recruiting neutrophils to sites of acute and chronic tissue inflammation. In transgenic mice, elevated serum IL-8 levels ranging from 1 to 118 ng/ml were correlated with proportional increases in circulating neutrophils and proportional decreases in L-selectin expression on the surface of blood neutrophils. No change in the expression of the beta 2-integrins Mac-1 and LFA-1 was apparent on peripheral blood neutrophils of the IL-8 transgenic mice. Additionally, L-selectin expression on bone marrow neutrophils and neutrophil precursors was normal in all transgenic lines. IL-8 transgenic mice demonstrated an accumulation of neutrophils in the microcirculation of the lung, liver and spleen. Moreover, there was no evidence of neutrophil extravasation, plasma exudation or tissue damage in any IL-8 transgenic mice. Neutrophil migration into the inflamed peritoneal cavity was severely inhibited in IL-8 transgenic mice, but not in nontransgenic littermates. The IL-8 transgenic mice should serve as useful models for studying the putative role of neutrophils in mediating tissue damage in models of inflammation, such as hepatic ischemia and reperfusion injury, cecal puncture and ligation, and glomerulonephritis.
Simonet
W S
WS
Department of Developmental Biology, Amgen Center, Thousand Oaks, California 91320.
Hughes
T M
TM
Nguyen
H Q
HQ
Trebasky
L D
LD
Danilenko
D M
DM
Medlock
E S
ES
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000097:blood; D002634:Chemotaxis, Leukocyte; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D007421:Intestine, Small / Q000378:metabolism; D007438:Introns; D019041:L-Selectin; D008099:Liver / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015183:Restriction Mapping
D000943:Antigens, Differentiation; D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D016209:Interleukin-8; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D019041:L-Selectin