Allograft inflammatory factor-1 is expressed by macrophages in injured skeletal muscle and abrogates proliferation and differentiation of satellite cells.
Secretion of regulatory peptides by macrophages in injured skeletal muscle constitutes a pivotal determinator of tissue homeostasis. We analyzed expression of a novel Ca2+- binding peptide expressed by activated macrophages, the allograft inflammatory factor-1 (AIF-1), in rat devascularized skeletal muscle. AIF-1 expression was observed in 94% of all macrophages at the site of the injury 48 hours postdevascularization. The physiological function of AIF-1 in injured skeletal muscle was analyzed using a rat in-vitro model of satellite cell proliferation and differentiation. Addition of AIF-1 to the culture medium resulted in a concentration-dependent and reversible reduction of the total number of cells expressing M-cadherin (p < or = 0.0001), a mediator of the differentiation process of skeletal muscle cells, the proliferation associated PCNA (p < or = 0.0001), and the initiator of muscle differentiation myogenin (p < or = 0.0001). These results provide convincing evidence that activated AIF-1 expressing macrophages constitute the predominant cell type in skeletal muscle 48 hours postinjury, and that AIF-1 regulates reduced proliferation, differentiation, and activation of satellite cells.
Kuschel
R
R
Institute of Brain Research, University of Tuebingen Medical School, Germany.
Deininger
M H
MH
Meyermann
R
R
Bornemann
A
A
Yablonka-Reuveni
Z
Z
Schluesener
H J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018008:Myogenin / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology
C100745:Aif1 protein, rat; D000911:Antibodies, Monoclonal; D015820:Cadherins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; C503803:Myog protein, rat; D018008:Myogenin; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; C070896:M-cadherin