Effects of steroid hormones on human polymorphonuclear leukocyte lysosomes.
Lysosomal membrane stabilization has been proposed as a mechanism for the anti-inflammatory action of corticosteroid hormones. This hypothesis was based on studies with liver organelles. We studied the action of steroids on intact lysosomes isolated from human peripheral blood polymorphonuclear (PMN) leukocytes. Both androstenedione and progesterone, 10(-3)-10(-5) M, caused leakage of acid hydrolase markers from these organelles, thus resembling their effects on liver lysosomes. But none of the anti-inflammatory steroids tested protected organelle membranes from either detergent lysis (Triton X-100) or heat incubation (37 degrees C, 90 min). Hydrocortisone (HC), HC sodium succinate, HC acetate, HC hemisuccinate, prednisone, and dexamethasone were without detectable stabilizing activity at concentrations of 10(-3)-5 x 10(-8) M. Release of the lysosomal marker, beta-glucuronidase, was not retarded by any of the compounds studied. In addition, PMN leukocyte lysosomes isolated from human volunteers receiving prednisolone were not more stable than control organelles, nor did serum from steroid-treated humans protect intact lysosomes from detergent lysis. Variations in cholesterol and phospholipid contents of liver and PMN leukocyte lysosome membranes could possibly account for the different reactivity to corticosteroids observed. We believe that the anti-inflammatory activity of adrenal corticosteroids can best be explained by their inhibitory effects on cellular metabolism rather than by their direct interaction with lysosomal membranes.
D000135:Acid Phosphatase / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000735:Androstenedione / Q000494:pharmacology; D002458:Cell Fractionation; D003907:Dexamethasone / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000648:ultrastructure*; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D011241:Prednisone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D000735:Androstenedione; D011374:Progesterone; D003907:Dexamethasone; D000135:Acid Phosphatase; D005966:Glucuronidase; D011241:Prednisone; D006854:Hydrocortisone