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.

Doni, A., Musso, T., Morone, D., Bastone, A., Zambelli, V., Sironi, M., et al. (2015). An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. JOURNAL OF EXPERIMENTAL MEDICINE, 212(6), 905-925 [10.1084/jem.20141268].

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

ZAMBELLI, VANESSA;
2015

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.
Articolo in rivista - Articolo scientifico
Animals; Arteries; Blood Coagulation; C-Reactive Protein; Cell-Free System; Collagen; Female; Fibrin; Fibrinolysis; Gene Expression Regulation; Hydrogen-Ion Concentration; Immunity, Humoral; Immunity, Innate; Leukocytes; Liver; Lung Injury; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Nerve Tissue Proteins; Phenotype; Plasminogen; Protein Structure, Tertiary; Skin; Surface Plasmon Resonance; Thrombosis; Wound Healing; Immunology; Immunology and Allergy
English
2015
212
6
905
925
none
Doni, A., Musso, T., Morone, D., Bastone, A., Zambelli, V., Sironi, M., et al. (2015). An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. JOURNAL OF EXPERIMENTAL MEDICINE, 212(6), 905-925 [10.1084/jem.20141268].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/120749
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