Down-regulation of receptor antigen in leukotriene B4-induced chemotactic deactivation of human polymorphonuclear leucocytes.
Pretreatment of suspensions of human polymorphonuclear leucocytes (PMNL) with leukotriene B4 (LTB4) induces chemotactic deactivation, characterized by diminished expression of high-affinity LTB4 receptors and selectively decreased chemotactic responsiveness of the PMNL to LTB4. Rabbit anti-idiotypic antibodies (a-Id) to mouse monoclonal anti-LTB4, which bind to 60,000-80,000 molecular weight (MW) membrane protein of PMNL receptors for LTB4 in Western blots and block binding of [3H]LTB4 to high-affinity receptors of PMNL, detected a reduction in LTB4 receptor antigen during chemotactic deactivation. Loss of high-affinity receptors for LTB4 from the surface of PMNL deactivated by incubation with 10 nM LTB4 was significant after 1 min and after 20 min reached a mean maximum of 82% and 61%, respectively, as assessed by binding of [3H]LTB4 and a-Id. Inhibitors of PMNL proteases did not prevent the deactivation-induced decreases in surface receptors for LTB4. Disruption of deactivated PMNL and solubilization of membrane proteins failed to expose intracellular LTB4 receptors. Incubation of membranes isolated from PMNL with 100 nM LTB4 resulted in a loss of LTB4 receptors similar to that observed in intact PMNL. Changes in LTB4 receptor protein structure or membrane localization, rather than endocytosis or proteolysis, thus appear to explain the rapidly decreased expression of LTB4 receptors, which results from stimulus-specific deactivation.
Boggs
J M
JM
Department of Medicine, University of California Medical Center, San Francisco 94143-0724.
Koo
C H
CH
Goetzl
E J
EJ
D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D007975:Leukotriene B4 / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis*; D018102:Receptors, Leukotriene B4
D000888:Antibodies, Anti-Idiotypic; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4