Clearance of cell remnants and regeneration of injured muscle depend on soluble pattern recognition receptor PTX3

Michela Vezzoli, Clara Sciorati, Lara Campana, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Gianfranca Corna, Thierry Touvier, Alessandra Castiglioni, Annalisa Capobianco, Alberto Mantovani, Angelo A. Manfredi, Cecilia Garlanda, Patrizia Rovere-Querini

Research output: Contribution to journalArticlepeer-review

Abstract

The signals causing resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute. We analyzed the expression of PTX3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocyte infiltration and the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and PTX3-deficient mice. PTX3 expression was upregulated 3 d to 5 d after injury and restricted to the extracellular matrix. Cellular debris and leukocytes persisted in the muscle of PTX3-deficient mice for a long time after wild-type animals had healed. PTX3-deficient macrophages expressed receptors involved in apoptotic cell clearance and engulfed dead cells in vitro. Accumulation of cell debris in a proinflammatory microenvironment was not sufficient to elicit autoantibodies. We concluded that PTX3 generated in response to muscle injury prompts clearance of debris and termination of the inflammatory response.

Original languageEnglish
Pages (from-to)809-820
Number of pages12
JournalMolecular Medicine
Volume22
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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