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J Exp Med. 2015 Jun 1;212(6):905-25. doi: 10.1084/jem.20141268. Epub 2015 May 11.

An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.

Author information

  • 1Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy.
  • 2Department of Public Health and Microbiology, University of Turin, 10124 Turin, Italy.
  • 3Department of Molecular Biochemistry and Pharmachology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
  • 4Department of Health Science, University of Milano-Bicocca, 20126 Monza, Italy.
  • 5Department of Plastic Surgery, Burn Unit and Skin Bank, Centro Traumatologico Ortopedico (CTO) Hospital, 10126 Turin, Italy.
  • 6IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy.
  • 7IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy.
  • 8Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy IRCCS - Multimedica, 20099 Milan, Italy.
  • 9Department 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.
  • 10Istituto 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.

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.

© 2015 Doni et al.

PMID:
25964372
[PubMed - indexed for MEDLINE]
PMCID:
PMC4451130
Free PMC Article
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