Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation.
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 adjuvant-immunized 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 alpha 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 alpha 4-integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion.
Johnston
B
B
Department of Physiology & Biophysics, University of Calgary, Alberta, Canada.
Burns
A R
AR
Suematsu
M
M
Watanabe
K
K
Issekutz
T B
TB
Kubes
P
P
D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000276:immunology; D002630:Chemotactic Factors / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D002908:Chronic Disease; D006133:Growth Substances / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins