Production and release of platelet-activating factor by the injured heart-muscle cell (cardiomyocyte).
The potential of the injured heart-muscle cell (cardiomyocyte) to produce platelet-activating factor (PAF) has been evaluated. Beating rat myocytes in primary monolayer culture were used as the study-object, and metabolic inhibition served as the injury stimulus. Coincident with the development of irreversible injury, myocytes evidenced a rapid, net production of PAF which was sustained for some 3-6 h and reached, maximally, low-ng levels within approximately 0.5 h of injury. In the presence of serum, much of the PAF was released from the injured myocytes, whereas under serum-free conditions the PAF remained largely intracellular. Cardiomyocyte-derived PAF was pro-aggregatory to platelets and displayed the chromatographic properties and chemical reactivity of authentic PAF. However, PAF itself did not elicit myocyte injury, and a specific PAF antagonist could not attenuate the myocyte damage associated with metabolic inhibition. These results suggest that the cardiomyocyte may constitute a cellular source of PAF during heart injury, although the cell itself is not directly responsive to PAF.
Janero
D R
DR
Department of Pharmacology and Chemotherapy, Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Burghardt
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004789:Enzyme Activation; D006335:Heart Injuries / Q000378:metabolism; D050356:Lipid Metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D010743:Phospholipids; D010972:Platelet Activating Factor; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D002794:Choline