STEM-CELL FACTOR INDUCTION IS ASSOCIATED WITH MAST-CELL ACCUMULATION AFTER CANINE MYOCARDIAL-ISCHEMIA AND REPERFUSION

Background-Myocardial infarction is associated with an intense inflamm atory reaction leading to healing and scar formation. Because mast cel ls are a significant source of fibrogenic factors, we investigated mas t cell accumulation and regulation of stem cell factor (SCF), a potent growth and tactic factor for mast cells, in the healing myocardium. M ethods and Results-Using a canine model of myocardial ischemia and rep erfusion, we demonstrated a striking increase of mast cell numbers dur ing the healing phase of a myocardial infarction. Mast cell numbers st arted increasing after 72 hours of reperfusion, showing maximum accumu lation in areas of collagen deposition (12.0+/-2.6-fold increase; P<0. 01) and proliferating cell nuclear antigen (PCNA) expression. The majo rity of proliferating cells were identified as alpha-smooth muscle act in-positive myofibroblasts or factor VIII-positive endothelial cells. Mast cells did not appear to proliferate. Using a nuclease protection assay, we demonstrated induction of SCF mRNA within 72 hours of reperf usion. Immunohistochemical studies demonstrated that a subset of macro phages was the source of SCF immunoreactivity in the infarcted myocard ium. SCF protein was not found in endothelial cells and myofibroblasts , Intravascular tryptase-positive, FITC-avidin-positive, CD11b-negativ e mast cell precursors were noted in the area of healing and in the ca rdiac lymph after 48 to 72 hours of reperfusion. Conclusions-Mast cell s increase in number in areas of collagen deposition and PCNA expressi on after myocardial ischemia, The data provide evidence of mast cell p recursor infiltration into the areas of cellular injury. SCF is induce d in a subset of macrophages infiltrating the healing myocardium, We s uggest an important role for SCF in promoting chemotaxis and growth of mast cell precursors in the healing heart.