Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate.
We have studied how cytosolic free Ca2+ ([Ca2+]i) changes and phorbol myristate acetate (PMA) exposure affects ligand-independent cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Mere incubation primed neutrophils to double their binding of fMet-Leu-Phe. This spontaneous increase of peptide binding was unaffected by changes in the extracellular calcium concentration. However, depression of the [Ca2+]i totally abolished the increased binding of fMet-Leu-Phe. Scatchard-Plot analysis revealed that the observed increase of peptide binding was due to an increased number of receptors. Normalization of the [Ca2+]i in cells where it was initially depressed resulted in a slow but progressive increase in fMet-Leu-Phe binding. The rate of receptor recruitment could be enhanced by rapidly increasing the [Ca2+]i by addition of ionomycin. Addition of PMA to cells with near maximal receptor expression led to a marked reduction of fMet-Leu-Phe binding without affecting [Ca2+]i. These observations suggest the existence of a dual regulatory mechanism for up- and down-regulation of fMet-Leu-Phe receptors on the cell surface of human neutrophils.
D000634:Aminoquinolines / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000634:Aminoquinolines; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; C035739:Quin2; D002118:Calcium