Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response.
Human polymorphonuclear (PMN) leukocytes bound [3H]leukotriene B4 ([3H]-LTB4) specifically, as assessed by the displacement of 88% or more of the bound radioactivity by a 15,000-fold higher concentration of nonradioactive LTB4 or by micromolar concentrations of structural isomers of LTB4. The specific binding of [3H]LTB4 by PMN leukocytes was characterized by rapid association and dissociation, and was saturable at 800 nM LTB4. The results of computer analyses of the concentration dependence of binding of [3H]LTB4 were consistent with the expression of two classes of receptors having respective mean affinities of 3.9 X 10(-10) M and 6.1 X 10(-8) M and mean densities of 4.4 X 10(3) and 2.7 X 10(5) per PMN leukocyte. Structural isomers of LTB4 inhibited the binding of [3H]LTB4 to PMN leukocytes at concentrations similar to those required to elicit chemotaxis, while chemotactic peptides did not inhibit binding. PMN leukocytes that were deactivated by prior exposure to LTB4 lost high affinity binding sites selectively and concurrently with a reduction in the chemotactic response to LTB4. Chemotactic deactivation altered, but did not eliminate, the low affinity receptors for LTB4 and reduced only minimally the lysosomal degranulation elicited by LTB4. The high affinity receptors for LTB4 on normal human PMN leukocytes appear to transduce the chemotaxis evoked by LTB4 without substantially modifying lysosomal degranulation.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001667:Binding, Competitive; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000145:classification / Q000187:drug effects; D018102:Receptors, Leukotriene B4
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011956:Receptors, Cell Surface; D018102:Receptors, Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid