Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation.
The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin-B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.
D002449:Cell Aggregation / Q000187:drug effects; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors*; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D009113:Muramidase / Q000378:metabolism; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009842:Oligopeptides / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D002630:Chemotactic Factors; D009842:Oligopeptides; D003571:Cytochalasin B; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D009113:Muramidase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate