Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion

Nikolaos G. Frangogiannis, Jerry L. Perrard, Leonardo H. Mendoza, Alan R. Burns, Merry L. Lindsey, Christie M. Ballantyne, Lloyd H. Michael, C. Wayne Smith, Mark L. Entman

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Background - Myocardial infarction is associated with an intense inflammatory reaction leading to healing and scar formation. Because mast cells are a significant source of fibrogenic factors, we investigated mast cell accumulation and regulation of stem cell factor (SCF), a potent growth and tactic factor for mast cells, in the healing myocardium. Methods and Results - Using a canine model of myocardial ischemia and reperfusion, we demonstrated a striking increase of mast cell numbers during the healing phase of a myocardial infarction. Mast cell numbers started increasing after 72 hours of reperfusion, showing maximum accumulation in areas of collagen deposition (12.0±2.6-fold increase; P<0.01) and proliferating cell nuclear antigen (PCNA) expression. The majority of proliferating cells were identified as α-smooth muscle actin-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 reperfusion. Immunohistochemical studies demonstrated that a subset of macrophages was the source of SCF immunoreactivity in the infarcted myocardium. SCF protein was not found in endothelial cells and myofibroblasts. Intravascular tryptase-positive, FITC-avidin-positive, CD11b- negative mast cell precursors were noted in the area of healing and in the cardiac lymph after 48 to 72 hours of reperfusion. Conclusions - Mast cells increase in number in areas of collagen deposition and PCNA expression after myocardial ischemia. The data provide evidence of mast cell precursor infiltration into the areas of cellular injury. SCF is induced in a subset of macrophages infiltrating the healing myocardium. We suggest an important role for SCF in promoting chemotaxis and growth of mast cell precursors in the healing heart.

Original languageEnglish (US)
Pages (from-to)687-698
Number of pages12
JournalCirculation
Volume98
Issue number7
DOIs
StatePublished - Aug 18 1998
Externally publishedYes

Keywords

  • Cells
  • Collagen
  • Growth substances
  • Myocardial infarction
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Frangogiannis, N. G., Perrard, J. L., Mendoza, L. H., Burns, A. R., Lindsey, M. L., Ballantyne, C. M., Michael, L. H., Smith, C. W., & Entman, M. L. (1998). Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation, 98(7), 687-698. https://doi.org/10.1161/01.CIR.98.7.687