Complement C1s activation in degenerating articular cartilage of rheumatoid arthritis patients: immunohistochemical studies with an active form specific antibody.
OBJECTIVE
The first complement component C1s was reported to have novel functions to degrade matrix components, besides its activities in the classic complement pathway. This study explores participation of C1s in articular cartilage degradation in rheumatoid arthritis (RA).


METHODS
Normal articular cartilage (n = 6) and cartilage obtained from joints with RA (n = 15) and osteoarthritis (OA, n = 10) were immunostained using anti-C1s monoclonal antibodies PG11, which recognises both active and inactive C1s, and M241, which is specifically reactive to activated C1s. The effects of inflammatory cytokines on C1s production by human articular chondrocytes were also examined by sandwich ELISA.


RESULTS
In normal articular cartilage, C1s was negative in staining with both PG11 and M241. In contrast, degenerating cartilage of RA was stained with PG11 (14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was activated as revealed by M241 staining. In OA, C1s staining was restricted in severely degrading part of cartilage (5 of 10 cases), and even in that part C1s was not activated. In addition, C1s production by chondrocytes in vitro was increased by an inflammatory cytokine, tumour necrosis factor alpha.


CONCLUSIONS
These results suggest that C1s activated in degenerative cartilage matrix of RA but not in that of OA. C1s is thought to participate in the pathogenesis of RA through its collagenolytic activity in addition to the role in the classic cascade.
Nakagawa
K
K
Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba, Japan.
Sakiyama
H
H
Tsuchida
T
T
Yamaguchi
K
K
Toyoguchi
T
T
Masuda
R
R
Moriya
H
H
D000293:Adolescent; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002358:Cartilage, Articular / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology; D003167:Complement Activation; D003172:Complement C1 / Q000032:analysis* / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003172:Complement C1; D014409:Tumor Necrosis Factor-alpha