Histamine release from human basophils by synthetic block co-polymers composed of polyoxyethylene and polyoxypropylene and synergy with immunologic and non-immunologic stimuli.
Co-polymers composed of polyoxyethylene and polyoxypropylene have been shown previously to trigger histamine release from mouse peritoneal mast cells; this property quantitatively is directly related to the ionophorous ability of these compounds to cause a functional exchange of intracellular K+ for extracellular Na+ across the cell membrane. We investigated the effect of an inflammatory copolymer, T130R2, on human basophils. The data demonstrate that T130R2 can cause calcium-dependent histamine release from human basophils in vitro. Further, at concentrations that do not cause histamine release, this co-polymer markedly augments release by suboptimal concentrations of the lectin Con A or anti-IgE antibody and the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate but not the calcium ionophore A23187. Thus, these co-polymers induce mediator release from cells of both rodents and humans. In both instances it is likely that calcium-dependent cell triggering is the result of an influx of sodium ions with concomitant depolarization of the transmembrane potential. In common with the calcium ionophore A23187, the co-polymer T130R2 has the ability to synergize with stimuli which trigger the IgE receptor as well as those which directly activate the cellular calcium- and phospholipid-dependent protein kinase.
Atkinson
T P
TP
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
Smith
T F
TF
Hunter
R L
RL
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001491:Basophils / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology; D011060:Poloxalene / Q000031:analogs & derivatives / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; C026408:anti-IgE antibodies; D003208:Concanavalin A; D007073:Immunoglobulin E; D000001:Calcimycin; D011092:Polyethylene Glycols; C035554:pluronic dibenzoyl ester; D011060:Poloxalene; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium