Histamine-releasing activity (HRA): III. HRA induces human basophil histamine release by provoking noncytotoxic granule exocytosis

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Histamine-releasing activity (HRA) is an ∼10,000–15,000 dalton, protease-sensitive factor that induces the rapid liberation of histamine from human basophils. Production of HRA by human peripheral blood mononuclear cells in vitro is augmented by concanavalin A or antigen, suggesting a mechanism whereby lymphocytes may regulate basophil mediator release in vivo. In order to determine whether HRA provokes conventional exocytosis of basophil granules or, alternatively, results in mediator release by some other mechanism such as vesicular transport or cytotoxicity, we investigated the ultrastructural features of human blood basophils purified over Percoll and exposed to HRA in vitro. HRA preparations induced a noncytotoxic pattern of basophil degranelation very similar to that previously observed in basophils triggered to release histamine in response to specific antigen, C5a, or mannitol. Thus, cytoplasmic granules were extruded singly hrough multiple separate points of fusion between perigranular membranes and the plasma membrane. Degranulating basophils exhibited plasma membrane activation but lacked a polarized configuration. By contrast, those basophils exposed to HRA that did not exhibit evidence of degranulation displayed a single elongated cellular process. The development of this polarized cellular configuration, similar in some respects to that of uropod-bearing motile guinea pig basophils, may have reflected chemokinetic or chemotactic effects of preparations containing HRA activity.