title: Complement dependent amplification of the innate response to a cognate microbial ligand by the long pentraxin PTX3.
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.
authors.affiliation: Istituto Clinico Humanitas, Rozzano (Milan), Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Cotena
authors.forename: Virginia
authors.initials: V
authors.lastname: Maina
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Corvaia
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002097:C-Reactive Protein; D003165:Complement System Proteins; D015289:Leukotrienes; D008024:Ligands; D008070:Lipopolysaccharides; D011453:Prostaglandins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C078167:OMPA outer membrane proteins