Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1

Brent Johnston, Alan R. Burns, Makoto Suematsu, Thomas B. Issekutz, Richard C. Woodman, Paul Kubes

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the function of this chemokine in models with preexisting inflammation is not known. Therefore, MCP-1 was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-1 elicited increased leukocyte transendothelial migration in adjuvant- immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-1. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the α4-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion.

Original languageEnglish
Pages (from-to)1269-1276
Number of pages8
JournalJournal of Clinical Investigation
Volume103
Issue number9
Publication statusPublished - 1999 May

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Chemokine CCL2
Chemokine Receptors
Neutrophils
Leukocytes
Up-Regulation
Inflammation
Transendothelial and Transepithelial Migration
CC Chemokines
Antibodies
Emigration and Immigration
Chemokines
CCR Receptors
Mesentery
Chemotaxis
Vasculitis
Integrins
Monocytes
Histology
Flow Cytometry

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Johnston, B., Burns, A. R., Suematsu, M., Issekutz, T. B., Woodman, R. C., & Kubes, P. (1999). Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. Journal of Clinical Investigation, 103(9), 1269-1276.

Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. / Johnston, Brent; Burns, Alan R.; Suematsu, Makoto; Issekutz, Thomas B.; Woodman, Richard C.; Kubes, Paul.

In: Journal of Clinical Investigation, Vol. 103, No. 9, 05.1999, p. 1269-1276.

Research output: Contribution to journalArticle

Johnston, B, Burns, AR, Suematsu, M, Issekutz, TB, Woodman, RC & Kubes, P 1999, 'Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1', Journal of Clinical Investigation, vol. 103, no. 9, pp. 1269-1276.
Johnston, Brent ; Burns, Alan R. ; Suematsu, Makoto ; Issekutz, Thomas B. ; Woodman, Richard C. ; Kubes, Paul. / Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 9. pp. 1269-1276.
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