Modulation of histamine release from human basophils in vitro by physiological concentrations of zinc.
Zinc, at physiologic concentrations, inhibits in vitro histamine release from human basophils induced by several immunologic (i.e., antigen and anti-immunoglobulin E (IgE) and nonimmunologic [Ca++ ionophore A23187 and formylated tripeptide formyl-methionyl-leucyl-phenylalanine (f-met peptide)] stimuli in a dose-dependent manner. Inhibition begins at about 10(-6) (ionophore A23187, anti-IgE and antigen) or 10(-5) M (f-met peptide) and is maximum at 10(-4) M (80--100% inhibition of histamine release). The activity of zinc is about 25-fold greater with respect to ionophore A23187 (ID50 = 1.1 x 10(-6) M) than to f-met peptide-induced (ID50 = 4 x 10(-5) M) histamine release. Its activity on IgE-mediated histamine release is intermediate between these two extremes (ID50 = 9.7 x 10(-6) M). Zinc does not affect the first stage of histamine release but acts on the calcium-dependent second stage. It is a competitive antagonist of the action of Ca++ in histamine secretion induced by antigen, anti-IgE and f-met peptide (but not by A23187) with a dissociation constant of about 1.2 x 10(-5) M. The addition of colchicine with zinc fails to increase the inhibition caused by the ion alone, suggesting the two compounds work via a common mechanism of action. Deuterium oxide reversed, in a dose-dependent manner, the inhibition of histamine release caused by zinc. These results suggest that the effect of zinc on histamine release from human basophils may be related to its influence on the microtubule system, directly or via its interaction with calcium.
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D052179:Antigens, Plant; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D003903:Deuterium / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D066298:In Vitro Techniques; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009842:Oligopeptides / Q000494:pharmacology; D010940:Plant Proteins; D011058:Pollen / Q000494:pharmacology; D015032:Zinc / Q000502:physiology*
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D000888:Antibodies, Anti-Idiotypic; D052179:Antigens, Plant; D009842:Oligopeptides; D010940:Plant Proteins; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D000001:Calcimycin; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003903:Deuterium; D015032:Zinc; D003078:Colchicine; D002118:Calcium