Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. Regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor.
OBJECTIVE
To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA).


METHODS
MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse-transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages.


RESULTS
High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast-like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin-1 (IL-1) and tumor necrosis factor in vitro. IL-1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue.


CONCLUSIONS
Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.
Akahoshi
T
T
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Wada
C
C
Endo
H
H
Hirota
K
K
Hosaka
S
S
Takagishi
K
K
Kondo
H
H
Kashiwazaki
S
S
Matsushima
K
K
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013582:Synovial Fluid / Q000737:chemistry / Q000166:cytology; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha