Efficient osteoclast differentiation requires local complement activation.

Previous studies using blocking antibodies suggested that bone marrow (BM)-derived C3 is required for efficient osteoclast (OC) differentiation, and that C3 receptors are involved in this process. However, the detailed underlying mechanism and the possible involvement of other complement receptors remain unclear. In this report, we found that C3(-/-) BM cells exhibited lower RANKL/OPG expression ratios, produced smaller amounts of macrophage colony-stimulating factor and interleukin-6 (IL-6), and generated significantly fewer OCs than wild-type (WT) BM cells. During differentiation, in addition to C3, WT BM cells locally produced all other complement components required to activate C3 and to generate C3a/C5a through the alter-native pathway, which is required for efficient OC differentiation. Abrogating C3aR/C5aR activity either genetically or pharmaceutically suppressed OC generation, while stimulating WT or C3(-/-) BM cells with exogenous C3a and/or C5a augmented OC differentiation. Furthermore, supplementation with IL-6 rescued OC generation from C3(-/-) BM cells, and neutralizing antibodies to IL-6 abolished the stimulatory effects of C3a/C5a on OC differentiation. These data indicate that during OC differentiation, BM cells locally produce components, which are activated through the alternative pathway to regulate OC differentiation. In addition to C3 receptors, C3aR/C5aR also regulate OC differentiation, at least in part, by modulating local IL-6 production.

Serum adipsin levels in patients with seasonal allergic rhinitis: preliminary data.

BACKGROUND: Several studies have outlined a possible relationship between adipokines and respiratory allergic diseases. However, there are no data about a role for adipsin in allergic rhinitis. OBJECTIVE: The aim of the study was to evaluate the serum adipsin levels in patients with seasonal allergic rhinitis (SAR), subdivided into two sub-groups: treated or not treated with sublingual immunotherapy (SLIT), and in a group of healthy controls. METHODS: The study included 110 subjects; i) 24 SLIT-treated SAR patients, ii) 62 untreated SAR patients, and iii) 24 normal subjects. All subjects were consecutively evaluated. A skin prick test and blood sampling for assessing serum adipsin levels were performed in all subjects. RESULTS: Serum adipsin was increased in SAR patients, even though significant only in males. There was also a significant positive association between adipsin and adiponectin. CONCLUSION: This preliminary study reports that adipsin serum levels may be increased in some SAR patients, but further functional studies should be performed.