Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers.

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Abstract
The chemotactic factor receptor on leukocytes initiate several cellular responses including chemotaxis, lysosomal enzyme secretion and O2- production. The latter 2 responses required .apprx. 10-100 times more chemoattractant than was required for chemotaxis. The effects of membrane fluidizers on the binding characteristics and the functional activities of the oligopeptide fMet-Leu-Phe chemotactic factor receptor on polymorphonuclear leukocytes were determined. Fluidization was induced by aliphatic alcohols and monitored by diphenylhexatriene fluorescence polarization. Low doses of n-butanol (0.25%) and n-pentanol (0.1%) were nontoxic to the leukocytes but reduced their diphenylhexatriene-induced polarization, indicating increased membrane fluidity. At these doses of alcohols, the affinity of the fMet-Leu-Phe receptor was enhanced from Kd = 25.5 .+-. 7.6 nM to 5.2 .+-. 0.9 nM and 6.0 .+-. 0.9 nM, respectively. Chemotaxis was also increased, as indicated by the decrease, by a factor of .apprx. 1/3 in the ED50 for fMet-Leu-Phe, as well as by a 1.5-fold increase in the maximal distance of migration in the presence of 0.25% butanol or 0.1% pentanol. In contrast to chemotaxis, the alcohols depressed fMet-Leu-Phe stimulation of O2- production by 90%, although they had no effect on phorbol 12-myristate 13-acetate-induced O2- production. Secretion of lysozyme was also inhibited. The affinity of the fMet-Leu-Phe receptor was modulated by membrane fluidizers. The higher affinity state of the receptor induced by the alcohols was more efficient in transducing chemotactic signals but was deficient in mediating O2- production or secretion. The transduction mechanisms for the various biological activities of the chemotactic factor receptor are heterogeneous and can be differentially manipulated by membrane fluidizers.