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 language | English (US) |
|---|---|
| Pages (from-to) | 687-698 |
| Number of pages | 12 |
| Journal | Circulation |
| Volume | 98 |
| Issue number | 7 |
| State | Published - Aug 18 1998 |
| Externally published | Yes |
Fingerprint
Keywords
- Cells
- Collagen
- Growth substances
- Myocardial infarction
- Reperfusion
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=0032544187&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032544187&partnerID=8YFLogxK
M3 - Article
C2 - 9715862
AN - SCOPUS:0032544187
VL - 98
SP - 687
EP - 698
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 7
ER -