Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation

Brent Johnston, Alan R. Burns, Makoto Suematsu, Kazuyoshi Watanabe, Thomas B. Issekutz, Paul Kubes

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 supervised 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 α4-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 α4-integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion.

Original languageEnglish
Pages (from-to)109-118
Number of pages10
JournalMicrocirculation
Volume7
Issue number2
Publication statusPublished - 2000

Fingerprint

CXC Chemokines
Neutrophils
Inflammation
Emigration and Immigration
Transendothelial and Transepithelial Migration
Leukocytes
Antibodies
Integrins
CC Chemokines
Venules
Chemotaxis
Vasculitis
Chemokines
Adhesives
Phenotype

Keywords

  • Chemotaxis
  • Integrins
  • Neutrophils
  • Vasculitis
  • Video microscopy

ASJC Scopus subject areas

  • Genetics
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Johnston, B., Burns, A. R., Suematsu, M., Watanabe, K., Issekutz, T. B., & Kubes, P. (2000). Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation. Microcirculation, 7(2), 109-118.

Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation. / Johnston, Brent; Burns, Alan R.; Suematsu, Makoto; Watanabe, Kazuyoshi; Issekutz, Thomas B.; Kubes, Paul.

In: Microcirculation, Vol. 7, No. 2, 2000, p. 109-118.

Research output: Contribution to journalArticle

Johnston, B, Burns, AR, Suematsu, M, Watanabe, K, Issekutz, TB & Kubes, P 2000, 'Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation', Microcirculation, vol. 7, no. 2, pp. 109-118.
Johnston B, Burns AR, Suematsu M, Watanabe K, Issekutz TB, Kubes P. Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation. Microcirculation. 2000;7(2):109-118.
Johnston, Brent ; Burns, Alan R. ; Suematsu, Makoto ; Watanabe, Kazuyoshi ; Issekutz, Thomas B. ; Kubes, Paul. / Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation. In: Microcirculation. 2000 ; Vol. 7, No. 2. pp. 109-118.
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AB - 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 supervised 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 α4-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 α4-integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion.

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