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

被引：126

作者：

Doni, Andrea ^{[1
]}

Musso, Tiziana ^{[2
]}

Morone, Diego ^{[1
]}

Bastone, Antonio ^{[3
]}

Zambelli, Vanessa ^{[4
]}

Sironi, Marina ^{[1
]}

Castagnoli, Carlotta ^{[5
,6
]}

Cambieri, Irene ^{[5
,6
]}

Stravalaci, Matteo ^{[3
]}

Pasqualini, Fabio ^{[1
]}

Laface, Ilaria ^{[1
]}

Valentino, Sonia ^{[1
]}

Tartari, Silvia ^{[1
]}

Ponzetta, Andrea ^{[1
]}

Maina, Virginia ^{[1
]}

Barbieri, Silvia S. ^{[7
]}

Tremoli, Elena ^{[7
,8
]}

Catapano, Alberico L. ^{[8
,9
]}

Norata, Giuseppe D. ^{[8
,10
]}

Bottazzi, Barbara ^{[1
]}

Garlanda, Cecilia ^{[1
]}

Mantovani, Alberto ^{[1
,11
]}

机构：

[1] Humanitas Clin & Res Ctr, Ist Ricovero & Cura Carattere Sci IRCCS, I-20089 Milan, Italy

[2] Univ Turin, Dept Publ Hlth & Microbiol, I-10124 Turin, Italy

[3] IRCCS Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmachol, I-20156 Milan, Italy

[4] Univ Milano Bicocca, Dept Hlth Sci, I-20126 Monza, Italy

[5] Ctr Traumatol Ortoped CTO Hosp, Dept Plast Surg, Burn Unit, I-10126 Turin, Italy

[6] Ctr Traumatol Ortoped CTO Hosp, Skin Bank, I-10126 Turin, Italy

[7] IRCCS Ctr Cardiol Monzino, I-20138 Milan, Italy

[8] Univ Milan, Dept Pharmacol & Biomol Sci, I-20122 Milan, Italy

[9] IRCCS Multimed, I-20099 Milan, Italy

[10] Bassini Hosp, Ctr Study Atherosclerosis, SISA, I-20154 Milan, Italy

[11] Humanitas Univ, I-20089 Milan, Italy

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2015年 / 212卷 / 06期

基金：

欧洲研究理事会;

关键词：

LONG PENTRAXIN PTX3; C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; AMYLOID P-COMPONENT; PLASMINOGEN-ACTIVATOR; INNATE IMMUNITY; ENDOTHELIAL SELECTINS; VASCULAR INFLAMMATION; MICE DEFICIENT; RECEPTOR PTX3;

D O I：

10.1084/jem.20141268

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：905 / 925

页数：21

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