Effects of inflammatory agents on endothelial lysosomal fragility and their inhibition by anti-inflammatory drugs.

1. Endothelial cells from human umbilical veins were maintained in tissue culture. The fragility of lysosomal membranes were studied by microdensitometry. 2. Histamine (50 microM to 10 mM), 4-methylhistamine (100 nM to 10 mM) and dimaprit (100 nM to 10 mM) increased lysosomal fragility. 2-Thiazolylethylamine and 2-pyridylethylamine (100 nM to 10 mM) had no effect. 3. Prostaglandins E1 and E2 (3 nM to 30 microM) and prostaglandin F2 alpha (2 nM to 20 microM) had no direct effect. Low concentrations of prostaglandins E1 and E2 inhibited the fragility induced by histamine 100 microM. 4. Bradykinin (100 nM to 100 microM) decreased fragility. 5. The increase in fragility induced by histamine 100 microM or dimaprit 100 microM was inhibited by cimetidine (100 microM to 1 mM) but not by mepyramine (1 microM 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 microM, respectively. 7. Lignocaine (1 microM to 1 mM) had no direct effect and did not decrease histamine-induced fragility.