Complement Dependent Amplification of the Innate Response to a Cognate Microbial Ligand by the Long Pentraxin PTX3
- 1 November 2007
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 179 (9), 6311-6317
- https://doi.org/10.4049/jimmunol.179.9.6311
Abstract
The long pentraxin PTX3 is a fluid-phase pattern recognition receptor, which plays a nonredundant role in resistance against selected pathogens. PTX3 has properties similar to Abs; its production is induced by pathogen recognition, it recognizes microbial moieties, activates complement, and facilitates cellular recognition by phagocytes. The mechanisms responsible for the effector function of PTX3 in vivo have not been elucidated. OmpA, a major outer membrane protein of Gram-negative Enterobacteriaceae, is a microbial moiety recognized by PTX3. In the air pouch model, KpOmpA induces an inflammatory response, which is amplified by coadministration of PTX3 in terms of leukocyte recruitment and proinflammatory cytokine production. PTX3 did not affect the inflammatory response to LPS, a microbial moiety not recognized by PTX3. As PTX3 binds to C1q and modulates the activation of the complement cascade, we assessed the involvement of complement in the amplification of the response elicited by KpOmpA and PTX3. Experiments performed using cobra venom factor, C1-esterase inhibitor, and soluble complement receptor 1 indicate that PTX3 amplifies the inflammatory response to KpOmpA through complement activation. The results reported here demonstrate that PTX3 activates a complement-dependent humoral amplification loop of the innate response to a microbial ligand.Keywords
This publication has 28 references indexed in Scilit:
- Activation of the lectin pathway in murine lupus nephritisMolecular Immunology, 2005
- Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesisBlood, 2004
- PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophagesJournal of Leukocyte Biology, 2004
- Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cellsEuropean Journal of Immunology, 2003
- Outer membrane protein A renders dendritic cells and macrophages responsive to CCL21 and triggers dendritic cell migration to secondary lymphoid organsEuropean Journal of Immunology, 2003
- Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune responseNature, 2002
- Knockout of Pentraxin 3, a Downstream Target of Growth Differentiation Factor-9, Causes Female SubfertilityMolecular Endocrinology, 2002
- Prostaglandins and Leukotrienes: Advances in Eicosanoid BiologyScience, 2001
- Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte RecruitmentImmunity, 1997
- Soluble Human Complement Receptor Type 1: In Vivo Inhibitor of Complement Suppressing Post-Ischemic Myocardial Inflammation and NecrosisScience, 1990