HETEROGENEOUS EFFECTS OF PROTAMINE ON HUMAN MAST-CELLS AND BASOPHILS

To investigate the mechanisms of anaphylactoid reactions to protamine, we have examined the in vitro effects of increasing concentrations of protamine (10(-6)-3x10(-4) mol litre(-1)) on the release of preformed (histamine and tryptase) and de novo synthesized (peptide leukotriene C-4 (LTC4) or prostaglandin D-2 (PGD(2))) mediators from human basoph ils and mast cells isolated from lung parenchyma, heart, skin and syno vial tissues. Protamine 10(-6)-3x10(-4) mol litre(-1) induced release of histamine, but not de novo synthesis of LTC4 from basophils. At con centrations from 10(-5) to 3x10(-4) mol litre(-1) it induced histamine release from human heart (mean 6.5 (SEM 1.5)%), skin (17.7 (4.1)%) an d to a lesser extent from synovial mast cells, but not from lung mast cells. Protamine also caused the release of tryptase from heart mast c ells (12.8 (3.2) mu g/10(7) cells), but did not induce de novo synthes is of LTC4 and PGD(2) from lung and skin mast cells. In these experime nts cross-linking of IgE by anti-IgE caused release of LTC4 or PGD(2) from human basophils or mast cells. These results demonstrate that pro tamine acted as an incomplete secretagogue, causing the release of pre formed mediators from human basophils and mast cells.