Studies on the uptake, binding and metabolism of leukotriene B4 by human neutrophils.
Human polymorphonuclear granulocytes (PMN) generate the inflammatory mediator leukotriene B4 (LTB4) as a response to cell activation. In addition, PMN inactivate LTB4 by omega-oxidation resulting in the formation of 20-OH- and 20-COOH-LTB4. The transport of exogenous LTB4 to the metabolizing enzymes is mediated via high- and low-affinity receptor subsets. Uptake of [3H]LTB4 by the cells was carried out in a time-dependent fashion, reaching maximal values after 5 min of incubation. No additional uptake of [3H]LTB4 then occurred. Prestimulation of PMN with phorbol myristate acetate or sodium fluoride resulted in the loss of high- and low-affinity receptors. Deactivating concentrations of LTB4 specifically reduced the high-affinity receptor subset. Prestimulation of PMN with cytochalasin B or with the membrane fluidizer butanol shifted the low-affinity receptors to the high-affinity state. The polyene antibiotic amphotericin B shifted high-affinity receptors to the low-affinity subset. The changes in the receptor expression pattern correlated with the respective conversion rate of exogenously added LTB4. Our results suggest that the distribution of high- and low-affinity receptors is regulated by GTP-binding proteins, the activation of protein kinase C and the organization of the membrane bilayer. In this way, human neutrophils control the respective level of the lipid mediator LTB4.
Brom
J
J
Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, FRG.
König
W
W
D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters; D011971:Receptors, Immunologic / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D013755:Tetradecanoylphorbol Acetate
D010703:Phorbol Esters; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; C008876:phorbol-12,13-didecanoate; D013755:Tetradecanoylphorbol Acetate