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PMID: 10225970 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 103 ·No. 9 ·1999-05-00 ·Pages 1269-76

Johnston B, Burns AR, Suematsu M, Issekutz TB, Woodman RC, Kubes P

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 alpha4-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. J. Clin. Invest. 103:1269-1276 (1999).

MeSH Terms
Animals Cell Adhesion Cell Movement Chemokine CCL2/metabolism Chronic Disease Male Neutrophils/cytology,metabolism Rats Rats, Sprague-Dawley Receptors, Chemokine/metabolism Up-Regulation Vasculitis/metabolism
Chemicals
Chemokine CCL2 Receptors, Chemokine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Johnston B
Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Burns A R
Suematsu M
Issekutz T B
Woodman R C
Kubes P
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI5208
Published
1999-05-00
Pages
1269-76
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC408354
Subset
IM
Grants
NHLBI NIH HHS · P01 HL042550 · United States
NHLBI NIH HHS · HL-42550 · United States
External Links
PubMed source DOI: 10.1172/JCI5208 PMC Full Text View journal details
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