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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunol
2013 ; 190
(12
): 6423-33
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Roles of adipocytes and fibroblasts in activation of the alternative pathway of
complement in inflammatory arthritis in mice
#MMPMID23650618
Arend WP
; Mehta G
; Antonioli AH
; Takahashi M
; Takahashi K
; Stahl GL
; Holers VM
; Banda NK
J Immunol
2013[Jun]; 190
(12
): 6423-33
PMID23650618
show ga
The complement system is involved in mediation of joint damage in rheumatoid
arthritis, with evidence suggesting activation of both the classical and
alternative pathway (AP). The AP is both necessary and sufficient to mediate
collagen Ab-induced arthritis, an experimental animal model of immune
complex-induced joint disease. The AP in mice is dependent on MASP-1/3 cleavage
of pro-factor D (pro-FD) into mature factor D (FD). The objectives of the current
study were to determine the cells synthesizing MASP-1/3 and pro-FD in synovial
tissue. Collagen Ab-induced arthritis was studied in wild-type C57BL/6 mice, and
the localization of mRNA and protein for FD and MASP-1/3 in synovial adipose
tissue (SAT) and fibroblast-like synoviocytes (FLS) was determined using various
techniques, including laser capture microdissection. SAT was the sole source of
mRNA for pro-FD. Cultured differentiated 3T3 adipocytes, a surrogate for SAT,
produced pro-FD but no mature FD. FLS were the main source of MASP-1/3 mRNA and
protein. Using cartilage microparticles (CMPs) coated with anti-collagen mAb and
serum from MASP-1/3(-/-) mice as a source of factor B, pro-FD in 3T3 supernatants
was cleaved into mature FD by MASP-1/3 in FLS supernatants. The mature FD was
eluted from the CMP, and was not present in the supernatants from the incubation
with CMP, indicating that cleavage of pro-FD into mature FD by MASP-1 occurred on
the CMP. These results demonstrate that pathogenic activation of the AP can occur
in the joint through immune complexes adherent to cartilage and the local
production of necessary AP proteins by adipocytes and FLS.