ANGIOGENIC AND INFLAMMATORY RESPONSES FOLLOWING SKELETAL-MUSCLE INJURY ARE ALTERED BY IMMUNE NEUTRALIZATION OF ENDOGENOUS BASIC FIBROBLAST GROWTH-FACTOR, INSULIN-LIKE GROWTH-FACTOR-I AND TRANSFORMING GROWTH-FACTOR-BETA-1

Injured skeletal muscle degeneration comprises early microvascular cha nges 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 transfo rming growth factor beta-1 (TGF beta 1), by injecting specific anti-gr owth factor neutralizing antibodies into mouse extensor digitorum long us muscle at the time of injury (denervation and devascularization). F our days later, at the height of damaged myofiber phagocytosis, we ass essed quantitatively revascularization, phagocytic activity, arid infl ammation. The immune neutralization of bFGF reduced the number of capi llaries, macrophages and mast cells, and delayed necrotic myofiber pha gocytosis. The immune neutralization of IGF1 or TGF beta 1 promoted mu scle revascularization, macrophage infiltration and necrotic myofiber phagocytosis. While IGF1 neutralization reduced the number of mast cel ls and did not modify that of T-cells or neutrophils, TGF beta 1 neutr alization increased the number of all of these cells. This study stron gly suggests differing roles for bFGF, IGF1 and TGF beta 1 in angiogen ic and inflammatory responses during muscle degeneration, apart from t heir known effects on the behaviour of myogenic cells.