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Increased Sensitivity to the C‐X‐C Chemokine CINC/gro in a Model of Chronic Inflammation
Author(s) -
Johnston Brent,
Burns Alan R.,
Suematsu Makoto,
Watanabe Kazuyoshi,
Issekutz Thomas B.,
Kubes Paul
Publication year - 2000
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1038/sj.mn.7300099
Subject(s) - inflammation , chemokine , sensitivity (control systems) , medicine , immunology , engineering , electronic engineering
Objective: The C‐C chemokine MCP‐1 elicits significant neutrophil emigration in rats with chronic adjuvant‐induced inflammation, but not in naive animals. We examined responses to the C‐X‐C chemokine CINC/gro to determine whether this class of chemokine elicits altered neutrophil responses during chronic inflammation. Methods: CINC/gro was superfused over mesenteric venules of naive rats or animals with chronic adjuvant‐induced vasculitis. Antibodies were used to characterize adhesive mechanisms. Results: CINC/gro elicited leukocyte transendothelial migration in adjuvantimmunized rats at 100‐fold lower concentrations than required to elicit transmigration in naive animals. In both groups, neutrophils constituted >95% of the leukocytes recruited by CINC/gro. Using in vitro chemotaxis assays, neutrophils from control and adjuvant‐immunized rats responded equally to CINC/gro, suggesting differences in migration were not related to neutrophil phenotype. Differences in adhesion molecule usage were noted in vivo . In control animals, CD18 antibodies blocked CINC/gro‐induced neutrophil adhesion and emigration. In adjuvant‐immunized animals, an α 4 ‐integrin antibody reduced adhesion and emigration, while a CD18 antibody selectively inhibited emigration. Conclusions: This study demonstrates increased sensitivity to a C‐X‐C chemokine in a model of chronic inflammation, implicates the α 4 ‐integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion.