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PMID: 1522232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.

The Journal of clinical investigation ·Vol. 90 ·No. 3 ·1992-09-00 ·Pages 772-9

Koch AE, Kunkel SL, Harlow LA, Johnson B, Evanoff HL, Haines GK, Burdick MD, Pope RM, Strieter RM

Abstract

Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine.

MeSH Terms
Arthritis, Rheumatoid/metabolism Base Sequence Chemokine CCL2 Chemotactic Factors/analysis,biosynthesis,genetics Fibroblasts/metabolism Humans Immunohistochemistry Interleukin-8/analysis Macrophages/metabolism Molecular Sequence Data RNA, Messenger/analysis Synovial Fluid/metabolism
Chemicals
Chemokine CCL2 Chemotactic Factors Interleukin-8 RNA, Messenger
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Koch A E
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Kunkel S L
Harlow L A
Johnson B
Evanoff H L
Haines G K
Burdick M D
Pope R M
Strieter R M
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115950
Published
1992-09-00
Pages
772-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC329929
Subset
IM
Grants
NIAMS NIH HHS · AR30692 · United States
NIAMS NIH HHS · AR41492 · United States
NHLBI NIH HHS · HL-02401 · United States
External Links
PubMed source DOI: 10.1172/JCI115950 PMC Full Text View journal details
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