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

144 Citations (Scopus)

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
StatePublished - Aug 18 1998
Externally publishedYes

Fingerprint

Myocardial Reperfusion
Stem Cell Factor
Mast Cells
Myocardial Ischemia
Canidae
Reperfusion
Myocardium
Myofibroblasts
Proliferating Cell Nuclear Antigen
Collagen
Nuclease Protection Assays
Endothelial Cells
Cell Count
Macrophages
Myocardial Infarction
Tryptases
Factor VIII
Lymph
Chemotaxis
Cicatrix

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Frangogiannis, N. G., Perrard, J. L., Mendoza, L. H., Burns, A. R., Lindsey, M. L., Ballantyne, C. M., ... 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.

Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. / Frangogiannis, Nikolaos G.; Perrard, Jerry L.; Mendoza, Leonardo H.; Burns, Alan R.; Lindsey, Merry L.; Ballantyne, Christie M.; Michael, Lloyd H.; Smith, C. Wayne; Entman, Mark L.

In: Circulation, Vol. 98, No. 7, 18.08.1998, p. 687-698.

Research output: Contribution to journalArticle

Frangogiannis, NG, Perrard, JL, Mendoza, LH, Burns, AR, Lindsey, ML, Ballantyne, CM, Michael, LH, Smith, CW & Entman, ML 1998, 'Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion', Circulation, vol. 98, no. 7, pp. 687-698.
Frangogiannis NG, Perrard JL, Mendoza LH, Burns AR, Lindsey ML, Ballantyne CM et al. Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation. 1998 Aug 18;98(7):687-698.
Frangogiannis, Nikolaos G. ; Perrard, Jerry L. ; Mendoza, Leonardo H. ; Burns, Alan R. ; Lindsey, Merry L. ; Ballantyne, Christie M. ; Michael, Lloyd H. ; Smith, C. Wayne ; Entman, Mark L. / Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. In: Circulation. 1998 ; Vol. 98, No. 7. pp. 687-698.
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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.",
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T1 - Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion

AU - Frangogiannis, Nikolaos G.

AU - Perrard, Jerry L.

AU - Mendoza, Leonardo H.

AU - Burns, Alan R.

AU - Lindsey, Merry L.

AU - Ballantyne, Christie M.

AU - Michael, Lloyd H.

AU - Smith, C. Wayne

AU - Entman, Mark L.

PY - 1998/8/18

Y1 - 1998/8/18

N2 - 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.

AB - 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.

KW - Cells

KW - Collagen

KW - Growth substances

KW - Myocardial infarction

KW - Reperfusion

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C2 - 9715862

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