Apoptosis of macrophages during the resulution of muscle inflammation.
We tested the hypothesis that apoptosis contributes to the depletion of macrophages expressing the ED1 or ED2 antigen during the resolution of rat muscle inflammation. Muscle inflammation was induced by subjecting rat soleus muscle to 10 days of unloading followed by periods of muscle reloading. Terminal deoxynucleotidyl transferase- mediated deoxyuridine triphosphate (dUTP) labeling of apoptotic nuclei showed that apoptotic inflammatory cells increase in concentration within necrotic fibers and in the connective tissue at 2 days following muscle injury caused by increased loading. Four days following injury, the apoptotic cells within damaged fibers returned to control levels, and at 7 days following injury apoptotic cells in the connective tissue returned to control concentrations. No preferential, internucleosomal cleavage of DNA from inflamed muscle was observed, although there was greater fragmentation of DNA in inflamed muscle than in controls. Double labeling studies show that cells expressing either ED1 or ED2 antigen can undergo apoptosis in vivo. The time course of apoptosis and concentration of apoptotic cells within damaged muscle fibers indicates that apoptosis contributes to returning ED1+ cells to control concentration during the resolution of inflammation. However, apoptosis of ED2+ cells during the first week following injury is not sufficient to return ED2+ cell concentrations to control values.
Tidball
J G
JG
Department of Physiological Science, University of California, Los Angeles, USA.
St Pierre
B A
BA
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis; D003238:Connective Tissue / Q000276:immunology / Q000473:pathology; D004249:DNA Damage; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009135:Muscular Diseases / Q000276:immunology* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015214:Antigens, Differentiation, Myelomonocytic; D008562:Membrane Glycoproteins