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


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 alpha-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.
Frangogiannis
N G
NG
The Methodist Hospital and The DeBakey Heart Center, Department of Medicine, Baylor College of Medicine, Houston, Tex 77030-3498, USA.
Perrard
J L
JL
Mendoza
L H
LH
Burns
A R
AR
Lindsey
M L
ML
Ballantyne
C M
CM
Michael
L H
LH
Smith
C W
CW
Entman
M L
ML
D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D003094:Collagen / Q000096:biosynthesis; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005169:Factor VIII / Q000032:analysis; D005260:Female; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology*; D015425:Myocardial Reperfusion; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000096:biosynthesis*; D013997:Time Factors
D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D005169:Factor VIII; D003094:Collagen