Stimulus response coupling in the human neutrophil. I. Kinetic analysis of changes in calcium permeability.
The relationship between receptor-ligand interaction in human neutrophils and initiation of enhanced Ca permeability ("45Ca uptake") has been correlated with cell function. Different ligands varied in their efficacy in provoking 45Ca permeability changes: chemotactic peptide f-Met-Leu-Phe greater than concanavalin A greater than immune complexes greater than phorbol myristate acetate. Mixtures of stimuli at optimal concentrations elicited no summation of responses, indicating that interaction of f-Met-Leu-Phe, concanavalin A, and phorbol myristate acetate with their respective "receptors" regulates a common site of 45Ca uptake. The onset of Ca uptake was an early event, preceding onset of aggregation, O-2 generation, and degranulation. Enhanced 45Ca permeability during neutrophil activation is dependent on mobilization of intracellular Ca, since 8-(N,N-diethylamino)-octyl:3,4,5-trimethoxybenzoate hydrochloride was a potent inhibitor of the Ca permeability response. In contrast, calmodulin antagonists did not inhibit Ca permeability changes; the requirement for calmodulin in the physiological responses of aggregation, O-2 generation, and degranulation must therefore be subsequent to activation of the "Ca translocator." We propose a role for a "Ca-translocating mechanism" as an amplifying factor in neutrophil activation.
D000936:Antigen-Antibody Complex; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D002463:Cell Membrane Permeability; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D003208:Concanavalin A; D013481:Superoxides; D014268:Trifluoperazine; D012710:Serum Albumin, Bovine; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium