Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers

Macrophage‐muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles...

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Published in:	Journal of leukocyte biology Vol. 69; no. 3; pp. 482 - 489
Main Authors:	Sandri, Marco, Sandri, Claudia, Brun, Barbara, Giurisato, Emanuele, Cantini, Marcello, Rossini, Katia, Destro, Chiara, Arslan, Paola, Carraro, Ugo
Format:	Journal Article
Language:	English
Published:	United States Society for Leukocyte Biology 01-03-2001
Subjects:	Animals apoptosis Apoptosis - physiology Cell Communication - physiology Cell Survival - physiology Coculture Techniques differentiation Fas Ligand Protein fas Receptor - physiology FasL protein Immunoglobulins - immunology inflammation Macrophages - cytology Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - immunology Membrane Glycoproteins - physiology Mice Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - metabolism Muscle Fibers, Skeletal - physiology Muscle, Skeletal - metabolism Muscle, Skeletal - physiology myoblast Myositis - chemically induced Myositis - pathology Regeneration - physiology
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Summary:	Macrophage‐muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas‐Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas‐Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000±27,838 vs. 41,661±6848, p<0.01) and 10 days from injury (145,500±40,850 vs. 5000±1000, p<0.001). Myofiber regeneration was highly impaired (37±14 vs. 252±28, p<0.01). Apoptosis of phagocytic cells was absent during Fas‐Ig treatment (0.9±0.6 vs. 1300±150,p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas‐Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co‐expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast‐macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up‐regulate muscle regeneration.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0741-5400 1938-3673
DOI:	10.1189/jlb.69.3.482