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

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 col...

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Main Authors: Doni, A., Musso, T., Morone, D., Bastone, A., Zambelli, V., Sironi, M., Castagnoli, C., Cambieri, I., Stravalaci, M., Pasqualini, F., Laface, I., Valentino, S., Tartari, S., Ponzetta, A., Maina, V., Barbieri, S., Tremoli, E., Catapano, A., Norata, Giuseppe, Bottazzi, B., Garlanda, C., Mantovani, A.
Format: Journal Article
Published: Rockefeller University Press 2015
Online Access:http://hdl.handle.net/20.500.11937/55603
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author Doni, A.
Musso, T.
Morone, D.
Bastone, A.
Zambelli, V.
Sironi, M.
Castagnoli, C.
Cambieri, I.
Stravalaci, M.
Pasqualini, F.
Laface, I.
Valentino, S.
Tartari, S.
Ponzetta, A.
Maina, V.
Barbieri, S.
Tremoli, E.
Catapano, A.
Norata, Giuseppe
Bottazzi, B.
Garlanda, C.
Mantovani, A.
author_facet Doni, A.
Musso, T.
Morone, D.
Bastone, A.
Zambelli, V.
Sironi, M.
Castagnoli, C.
Cambieri, I.
Stravalaci, M.
Pasqualini, F.
Laface, I.
Valentino, S.
Tartari, S.
Ponzetta, A.
Maina, V.
Barbieri, S.
Tremoli, E.
Catapano, A.
Norata, Giuseppe
Bottazzi, B.
Garlanda, C.
Mantovani, A.
author_sort Doni, A.
building Curtin Institutional Repository
collection Online Access
description 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.
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publishDate 2015
publisher Rockefeller University Press
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spelling curtin-20.500.11937-556032017-09-13T16:11:25Z An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode Doni, A. Musso, T. Morone, D. Bastone, A. Zambelli, V. Sironi, M. Castagnoli, C. Cambieri, I. Stravalaci, M. Pasqualini, F. Laface, I. Valentino, S. Tartari, S. Ponzetta, A. Maina, V. Barbieri, S. Tremoli, E. Catapano, A. Norata, Giuseppe Bottazzi, B. Garlanda, C. Mantovani, A. 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 Journal Article http://hdl.handle.net/20.500.11937/55603 10.1084/jem.20141268 Rockefeller University Press unknown
spellingShingle Doni, A.
Musso, T.
Morone, D.
Bastone, A.
Zambelli, V.
Sironi, M.
Castagnoli, C.
Cambieri, I.
Stravalaci, M.
Pasqualini, F.
Laface, I.
Valentino, S.
Tartari, S.
Ponzetta, A.
Maina, V.
Barbieri, S.
Tremoli, E.
Catapano, A.
Norata, Giuseppe
Bottazzi, B.
Garlanda, C.
Mantovani, A.
An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title_full An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title_fullStr An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title_full_unstemmed An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title_short An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
title_sort acidic microenvironment sets the humoral pattern recognition molecule ptx3 in a tissue repair mode
url http://hdl.handle.net/20.500.11937/55603