| First Author | Dimitrova P | Year | 2012 |
| Journal | Arthritis Res Ther | Volume | 14 |
| Issue | 4 | Pages | R173 |
| PubMed ID | 22830570 | Mgi Jnum | J:329708 |
| Mgi Id | MGI:6832588 | Doi | 10.1186/ar3926 |
| Citation | Dimitrova P, et al. (2012) Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis. Arthritis Res Ther 14(4):R173 |
| abstractText | INTRODUCTION: Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). METHODS: Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and wild-type (WT) C57BL/6 mice. Symptoms of disease were evaluated daily. The degree of joint damage was assessed histologically and with immunostaining for bone-resorption markers. Phenotypes of cell populations, their receptor expression, and intracellular cytokine production were determined with flow cytometry. Osteoclast differentiation of bone marrow (BM) precursors was evaluated by staining for tartrate-resistant acid phosphatase (TRAP). RESULTS: Properdin-deficient mice developed less severe CAIA than did WT mice. They showed significantly improved clinical scores and downregulated expression of bone-resorption markers in the joints at day 10 of disease. The frequencies of Ly6G(+)CD11b(+) cells were fewer in BM, blood, and synovial fluid (SF) of KO than of WT CAIA mice. The receptor activator of nuclear factor kappaB ligand (RANKL) was downregulated on arthritic KO neutrophils from BM and the periphery. Decreased C5a amounts in KO SF contributed to lower frequencies of CD5aR(+)-bearing neutrophils. In blood, surface C5aR was detected on KO Ly6G(+) cells as a result of low receptor engagement. Circulating CD4(+) T cells had an altered ability to produce interleukin (IL)-17 and interferon (IFN)-gamma and to express RANKL. In KO CAIA mice, decreased frequencies of CD4(+) T cells in the spleen were related to low CD86 expression on Ly6GhighCD11b(+) cells. Arthritic KO T cells spontaneously secreted IFN-gamma but not IL-17 and IL-6, and responded to restimulation with less-vigorous cytokine production in comparison to WT cells. Fewer TRAP-positive mature osteoclasts were found in KO BM cell cultures. CONCLUSIONS: Our data show that the active involvement of properdin in arthritis is related to an increased proinflammatory cytokine production and RANKL expression on immune cells and to a stimulation of the RANKL-dependent osteoclast differentiation. |
