title: In vivo responses of macrophages and myofibroblasts in the healing following isoproterenol-induced myocardial injury in rats.
abstract: To clarify the relation between macrophage and myofibroblast involvement in various myocardial diseases, the authors investigated the kinetics of these cells in the healing (scar tissue formation) following isoproterenol-induced myocardial injury in rats. Alpha-smooth muscle actin (alpha-SMA) expressing myofibroblasts were seen at the border of the affected area and appeared in the greatest numbers on days 3-7 post-injection, followed by a gradual decrease by day 35. The peak on day 3 was consistent with the timing of the highest proliferative activity of myofibroblasts. The number of ED1-positive macrophages began to increase as early as day 1, reaching a peak on day 3 within the injured myocardium. The expansion of ED1-positive macrophages preceded an increased number of alpha-SMA-positive myofibroblasts suggesting that myofibroblast proliferation and activation may be mediated by factors released by ED1-positive macrophages in response to myocardial injury. The number of ED2-positive tissue-fixed, resident macrophages gradually, increased from day 3 post-injection, and peaked on day 14, but the number of ED2-positive macrophages was consistently fewer than that of ED1-positive macrophages during the 35 day-observation period after the injection. The labelling index of the ED2-positive cells was maximal on day 14, indicative of local proliferation of resident macrophages. In the healing process after myocardial injury, ED1-positive macrophages increase markedly in the early stages: ED2-positive macrophages appear later.
authors.affiliation: Laboratory of Toxicologic Pathology, Kanebo Limited, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakatsuji
authors.forename: J
authors.initials: J
authors.lastname: Yamate
authors.forename: M
authors.initials: M
authors.lastname: Kuwamura
authors.forename: T
authors.initials: T
authors.lastname: Kotani
authors.forename: S
authors.initials: S
authors.lastname: Sakuma
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006335:Heart Injuries / Q000139:chemically induced* / Q000276:immunology; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D007545:Isoproterenol