Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes.

Abstract

The binding of nanomolar concentrations of [3H]leukotriene [LT] B4 to human polymorphonuclear leukocytes [PMN] is described. Because up to 80% of the total [3H]LTB4 binding was blocked by excess (> 100 times) [14C]LTB4, the majority of binding is specific. Stereospecificity of the LTB4 binding is demonstrated by the diminished relative abilities of the 6-trans- and 12-epi-6-trans-isomers of LTB4 to block [3H]LTB4 binding. With these 2 isomers, 3- to 10-fold higher than [14C]LTB4 concentrations were needed for equivalent inhibition of [3H]LTB4 binding. This difference is quantitatively less dramatic than the differences between these isomers in many in vitro functional assays, such as chemokinesis, chemotaxis and degranulation. Binding of [3H]FMLP [N-formyl-methionyl-leucyl-phenylalanine] is not blocked at > 100-fold excess of LTB4. The binding of [3H]LTB4 to cells appears to be essentially irreversible at 4.degree. C, but not at 37.degree. C, where initially bound LTB4 is rapidly converted to metabolites which then enter the medium. The presence of a saturable, stereospecific site for LTB4 on PMN is suggested. The association of LTB4 binding and the initiation of pharmacological responses to LTB4 will require further studies.