M. Arras et al., TUMOR-NECROSIS-FACTOR-ALPHA IS EXPRESSED BY MONOCYTES MACROPHAGES FOLLOWING CARDIAC MICROEMBOLIZATION AND IS ANTAGONIZED BY CYCLOSPORINE/, Basic research in cardiology, 93(2), 1998, pp. 97-107
The time course of expression of TNF-alpha in myocardial wound healing
following ischemic injury was investigated in the porcine heart. Micr
oembolization was used to induce focal ischemia and necrosis in hearts
of 39 adult pigs. The animals were sacrified after 3, 6, 12, 24 h, 3
and 7 days, and after 4 weeks, and the myocardial tissue was studied b
y immunofluorescence using specific antibodies. TNF-alpha containing c
ells were identified as monocytes/macrophages by double staining with
a muramidase antibody. Monocytes/macrophages were the only source of T
NF-alpha. Microembolization caused multiple necrotic foci with loss of
myocytes in the left ventricular myocardium. These foci contained num
erous monocytes/macrophages and showed an inflammatory reaction typica
l of wound healing followed by replacement with scar tissue. The numbe
r of TNF-alpha positive cells increased after 24 h, peaked between 3-7
days and slowly decreased thereafter. Expression of TNF-alpha in mono
cytes/macrophages was significantly reduced after pretreatment of pigs
with cyclosporine or dexamethasone. It is concluded that 1.) in myoca
rdial tissue monocytes/macrophages are the only cell type expressing T
NF-alpha, 2.) TNF-alpha is involved in wound healing after ischemia, a
nd 3.) synthesis of TNF-alpha and inflammatory angiogenesis can be inh
ibited be treatment with either cyclosporine or dexamethasone.