EFFECTS OF INFLAMMATORY AGENTS ON ENDOTHELIAL LYSOSOMAL FRAGILITY AND THEIR INHIBITION BY ANTIINFLAMMATORY DRUGS

Abstract

1 Endothelial cells from human unbilical veins were maintained in tissue culture. The fragility of lysosomal membranes were studied by microdensitometry. 2 Histamine (50 μm to 10 mm), 4-methylhistamine (100 nm to 10 mm) and dimaprit (100 nm to 10 mm) increased lysosomal fragility. 2-Thiazolyethylamine and 2-pyridylethylamine (100 nm to 10 mm) had no effect. 3 Prostaglandins E₁ and E₂ (3 nm to 30 μm) and prostaglandin F_2α (2 nm to 20 μm) had no direct effect. Low concentrations of prostaglandins E₁ and E₂ inhibited the fragility induced by histamine 100 μm. 4 Bradykinin (100 nm to 100 μm) decreased fragility. 5 The increase in fragility induced by histamine 100 μm or dimaprit 100 μm was inhibited by cimetidine (100 μm and 1 mm) but not by mepyramine (1 μm to 1 mm). 6 Pretreatment with indomethacin, hydrocortisone, ibuprofen and sodium salicylate caused a dose-dependent inhibition of histamine-induced fragility. Threshold concentrations were 1 pm, 100 pm, 10 nm and 10 μm, respectively. 7 Lignocaine (1 μm to 1 mm) had no direct effect and did not decrease histamine-induced fragility.