Angiogenic and inflammatory responses following skeletal muscle injury are altered by immune neutralization of endogenous basic fibroblast growth factor, insulin-like growth factor-1 and transforming growth factor-beta 1.
Injured skeletal muscle degeneration comprises early microvascular changes and inflammatory cell infiltration, possibly under the control of several growth factors. We have studied the role of basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF1), and transforming growth factor beta-1 (TGF beta 1), by injecting specific anti-growth factor neutralizing antibodies into mouse extensor digitorum longus muscle at the time of injury (denervation and devascularization). Four days later, at the height of damaged myofiber phagocytosis, we assessed quantitatively revascularization, phagocytic activity, and inflammation. The immune neutralization of bFGF reduced the number of capillaries, macrophages and mast cells, and delayed necrotic myofiber phagocytosis. The immune neutralization of IGF1 or TFG beta 1 promoted muscle revascularization, macrophage infiltration and necrotic myofiber phagocytosis. While IGF1 neutralization reduced the number of mast cells and did not modify that of T-cells or neutrophils, TGF beta 1 neutralization increased the number of all of these cells. This study strongly suggests differing roles for bFGF, IGF1 and TFG beta 1 in angiogenic and inflammatory responses during muscle degeneration, apart from their known effects on the behaviour of myogenic cells.
Lefaucheur
J P
JP
Laboratoire de Physiologie, Atelier de Régénération Neuro-musculaire, Faculté de Médecine Saint-Antoine, Paris, France.
Gjata
B
B
Lafont
H
H
Sebille
A
A
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000502:physiology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000098:blood supply / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D009220:Myositis / Q000209:etiology / Q000503:physiopathology*; D009336:Necrosis; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009504:Neutrophils / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D012038:Regeneration; D013601:T-Lymphocytes / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects*
D000906:Antibodies; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I