The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells

Journal of Leukocyte Biology

Alberto Mantovani³  Giuseppe Peri⁴  Ingrid E. Dumitriu⁵  Paramita Baruah⁵  Patrizia Rovere-Querini⁵  Angelo A. Manfredi²  Vincenzo Russo¹ 

[1] Cancer Gene Therapy Unit, Cancer Immunotherapy & Gene Therapy Program, H. San Raffaele Scientific Institute, Milano, Italy; Cancer Gene Therapy Unit, Cancer Immunotherapy & Gene Therapy Program, H. San Raffaele Scientific Institute, Milano, Italy; Cancer Gene Therapy Unit, Cancer Immunotherapy & Gene Therapy Program, H. San Raffaele Scientific Institute, Milano, Italy;;Clinical Immunology Unit and Vita-Salute San Raffaele University, Milano, Italy Clinical Immunology Unit and Clinical Immunology Unit and Vita-Salute San Raffaele University, Milano, Italy Vita-Salute San Raffaele University, Milano, Italy Clinical Immunology Unit and Vita-Salute San Raffaele University, Milano, Italy;Istituto Clinico Humanitas, Rozzano, Italy; Centro di Eccellenza per l’Innovazione Diagnostica e Terapeutica (IDET), Institute of General Pathology, University of Milan, Italy; and Istituto Clinico Humanitas, Rozzano, Italy; Istituto Clinico Humanitas, Rozzano, Italy; Centro di Eccellenza per l’Innovazione Diagnostica e Terapeutica (IDET), Institute of General Pathology, University of Milan, Italy; and Centro di Eccellenza per l’Innovazione Diagnostica e Terapeutica (IDET), Institute of General Pathology, University of Milan, Italy; and Istituto Clinico Humanitas, Rozzano, Italy; Centro di Eccellenza per l’Innovazione Diagnostica e Terapeutica (IDET), Institute of General Pathology, University of Milan, Italy; andIstituto Clinico Humanitas, Rozzano, Italy; Istituto Clinico Humanitas, Rozzano, Italy; Istituto Clinico Humanitas, Rozzano, Italy;;Clinical Immunology Unit and Clinical Immunology Unit and Clinical Immunology Unit and

关键词: Toll-like receptor;    systemic lupus erythematosus;    lipopolysaccharide;    apoptosis;    inflammation;   

DOI  :  10.1189/jlb.0805445

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Pentraxins (PTX) and complement belong to the humoral arm of the innate immune system and have essential functions in immune defense to microbes and in scavenging cellular debris. The prototypic long PTX, PTX3, and the first component of the classical complement pathway, C1q, are innate opsonins involved in the disposal of dying cells by phagocytes. Whether the interaction between various innate opsonins impacts on their function is not fully understood. We show here that characterized Toll-like receptor (TLR) ligands elicit the production of C1q and PTX3 by immature dendritic cells (DC). Moreover, these molecules bind to dying cells with similar kinetics, although they recognize different domains on the cell membranes. PTX3 binds in the fluid phase to C1q, decreasing C1q deposition and subsequent complement activation on apoptotic cells. C1q increases the phagocytosis of apoptotic cells by DC and the release of interleukin-12 in the presence of TLR4 ligands and apoptotic cells; PTX3 inhibits both events. Moreover, PTX3 inhibited the cross-presentation of the MELAN-A/melanoma antigen-reactive T cell 1 (MART-1) tumor antigen expressed by dying cells, even in the presence of C1q. These results suggest that interaction of C1q and PTX3 influences the clearance of apoptotic cells by DC. The coordinated induction by primary, proinflammatory signals of C1q and PTX3 and their reciprocal regulation during inflammation influences the clearance of apoptotic cells by antigen-presenting cells and possibly plays a role in immune homeostasis.

【 授权许可】

Unknown