From the Section of Cardiovascular Sciences, The Methodist Hospital and
The DeBakey Heart Center, Department of Medicine, the Speros P. Martel
Laboratory, Section of Leukocyte Biology, Department of Pediatrics, and Texas
Children's Hospital, Baylor College of Medicine, Houston, Tex.
Correspondence to Mark L. Entman, MD, Department of Medicine, Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza, M/S F-602, Houston, TX 77030-3498. E-mail mentman{at}bcm.tmc.edu
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
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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Stem Cell Factor Induction Is Associated With Mast Cell Accumulation After Canine Myocardial Ischemia and Reperfusion
-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.
Key Words: cells • collagen • myocardial infarction • reperfusion • growth substances
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