Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis.
Chemokines are mediators of innate and acquired immunity. CCL18, also designated pulmonary and activation-regulated chemokine (PARC), dendritic cell-derived CC chemokine-1 (DC-CK1), alternative macrophage activation-associated CC chemokine-1 (AMAC-1) and macrophage inflammatory protein-4 (MIP-4), was for the first time isolated from peripheral blood mononuclear cells (PBMC) and biochemically characterized. We found that CCL18/PARC protein is spontaneously secreted by PBMC and is selectively induced in PBMC by staphylococcal enterotoxins (SEA, SEB) and IL-4, but not by IFN-gamma and the CXCL8/IL-8 inducers lipopolysaccharide (LPS) or Concanavalin A. Human fibroblasts, chondrocytes and endothelial cells did not produce CCL18/PARC in response to inflammatory mediators such as measles virus, double-stranded RNA, LPS or IL-1beta, whereas up to 150 ng/ml of CCL2/MCP-1 was induced under these conditions. In synovial fluids from septic and rheumatoid arthritis patients, fourfold-enhanced CCL18/PARC levels (150 ng/ml) were detected compared to those in crystal-induced arthritis and osteoarthritis. In septic arthritis, the synovial levels of CCL18/PARC were fivefold higher than those of CXCL8/IL-8. Immunochemistry revealed CD68(+) monocytes/macrophages as the main CCL18/PARC-producing cell type in both PBMC and arthritic synovial tissue. In addition, CD1a(+) blood dendritic cells expressed CCL18/PARC. These findings suggest that monocytic cells respond to Gram-positive bacterial infection by the production of CCL18/PARC in the synovial cavity.
Schutyser
E
E
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Struyf
S
S
Wuyts
A
A
Put
W
W
Geboes
K
K
Grillet
B
B
Opdenakker
G
G
Van Damme
J
J
D001170:Arthritis, Infectious / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D019742:Chemokines, CC / Q000096:biosynthesis*; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
C111792:CCL18 protein, human; D019742:Chemokines, CC; D004768:Enterotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal