Activated leucocytes express and secrete macrophage inflammatory protein-1alpha upon interaction with synovial fibroblasts of rheumatoid arthritis via a beta2-integrin/ICAM-1 mechanism.
OBJECTIVE
To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1alpha (MIP-1alpha) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients.


METHODS
Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1alpha by enzyme-linked immunosorbent assay. The expression of MIP-1alpha mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively.


RESULTS
Interaction of activated leucocytes with FLS synergistically increased MIP-1alpha expression and secretion via a mechanism mediated by beta2-integrin/ intercellular adhesion molecule 1.


CONCLUSIONS
MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.
Hanyuda
M
M
Showa University School of Medicine, Tokyo, Japan.
Kasama
T
T
Isozaki
T
T
Matsunawa
M M
MM
Yajima
N
N
Miyaoka
H
H
Uchida
H
H
Kameoka
Y
Y
Ide
H
H
Adachi
M
M
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D018821:CD18 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
D018821:CD18 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1