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Publication : Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus.

First Author  Moalli F Year  2010
Journal  Blood Volume  116
Issue  24 Pages  5170-80
PubMed ID  20829368 Mgi Jnum  J:167412
Mgi Id  MGI:4868182 Doi  10.1182/blood-2009-12-258376
Citation  Moalli F, et al. (2010) Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus. Blood 116(24):5170-80
abstractText  Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fcgamma receptor (FcgammaR) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common gamma chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common gamma chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and FcgammaR-mediated recognition. Because short pentraxins (eg, C-reactive protein) interact with complement and FcgammaR, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity.
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