title: An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.
abstract: Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.affiliation: Department of Public Health and Microbiology, University of Turin, 10124 Turin, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Morone
authors.affiliation: Department of Molecular Biochemistry and Pharmachology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bastone
authors.affiliation: Department of Health Science, University of Milano-Bicocca, 20126 Monza, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zambelli
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Department of Plastic Surgery, Burn Unit and Skin Bank, Centro Traumatologico Ortopedico (CTO) Hospital, 10126 Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Castagnoli
authors.affiliation: Department of Plastic Surgery, Burn Unit and Skin Bank, Centro Traumatologico Ortopedico (CTO) Hospital, 10126 Turin, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Cambieri
authors.affiliation: Department of Molecular Biochemistry and Pharmachology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Stravalaci
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laface
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Valentino
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tartari
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ponzetta
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Maina
authors.affiliation: IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Barbieri
authors.affiliation: IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy IRCCS - Multimedica, 20099 Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy Società Italiana per lo Studio della Arteriosclerosi (SISA) Center for the Study of Atherosclerosis, Bassini Hospital, 20154 Milan, Italy.
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Norata
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy Humanitas University, 20089 Milan, Italy alberto.mantovani@humanitasresearch.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D001777:Blood Coagulation; D002097:C-Reactive Protein / Q000378:metabolism*; D002474:Cell-Free System; D003094:Collagen / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D056724:Immunity, Humoral / Q000502:physiology*; D007113:Immunity, Innate; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000293:injuries; D055370:Lung Injury / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D010958:Plasminogen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012867:Skin / Q000276:immunology / Q000473:pathology; D020349:Surface Plasmon Resonance; D013927:Thrombosis / Q000473:pathology; D014945:Wound Healing; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D003094:Collagen; D005337:Fibrin; D009419:Nerve Tissue Proteins; D010958:Plasminogen; D000099153:Pentraxins