Abstract
The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute. We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and ptx3-deficient mice. Ptx3 expression was up-regulated three-five days 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 pro-inflammatory microenvironment was not sufficient to elicit autoantibodies. PTX3 generated in response to muscle injury prompts the clearance of debris and the termination of the inflammatory response.
Highlights
Pentraxins act as soluble pattern recognition molecules and are a component of the humoral arm of innate immunity [1,2]
PTX3 expression is upregulated in regenerating skeletal muscle upon acute sterile injury
We investigated in WT and PTX3-/- muscle the expression of molecules involved in the ability of macrophages to recognize and clear apoptotic cells
Summary
Pentraxins act as soluble pattern recognition molecules and are a component of the humoral arm of innate immunity [1,2]. C-reactive protein and serum amyloid P-component are acute phase proteins released in response to inflammatory signals [1]. PTX3 is the first identified member of the long pentraxin family; it contains a well-conserved pentraxin domain at the C terminus and a unique N-terminal sequence. Macrophages, neutrophils and dendritic cells produce and release PTX3 in response to inflammatory signals (eg, IL-1β and TNF-α) and Toll-like receptor activation [1,3]. The physiological functions attributed to pentraxins involve recognition and binding of different ligands: microbial moieties, complement components, apoptotic cell constituents, P-selectin and extracellular matrix proteins [4,5,6,7,8]
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