VARIABILITY OF IGE-DEPENDENT HISTAMINE-RELEASING ACTIVITY IN SUPERNATANTS OF HUMAN MONONUCLEAR-CELLS

Histamine-releasing factors (HRF) that release mediators from human ba sophils by interacting with IgE have been identified from different ce ll sources, including lymphocytes, monocytes, thrombocytes and endothe lial cells. These factors are studied in view of their potential impor tance as a stimulus in chronic inflammation. In this report we investi gated the qualitative variability of the histamine-releasing activity in the supernatants of activated mononuclear cells. Purified human mon onuclear cells of 8 donors were activated with streptokinase/streptodo rnase (SK/SD) and the supernatants (HRF-MN) were tested for histamine- releasing activity (HRA) in both allergic (RAST positive for inhalant allergens) and nonallergic individuals. Four of the eight HRF-MN super natants were discriminating, i.e. showing no histamine-release respons e with nonallergic individuals, whereas four supernatants were not. Tw o of the HRF-MN supernatants that exhibited discriminating properties were studied in more detail. The response to HRF-MN was tested (1) in a direct bioassay on basophils of allergic (RAST positive for inhalant allergens) and nonallergic individuals and (2) in an indirect bioassa y with 70% pure basophils of RAST-negative donors after passive sensit ization with sera of allergic donors. An association was found between the response to HRF-MN and the RAST for inhalant allergens: none (0/1 2) of the RAST-negative but 15/22 of the RAST-positive individuals wer e HRF-MN responders. The IgE dependency of HRF-MN was shown e.g. by in hibition of passive sensitization by preincubating a responder serum w ith monoclonal antibody (moAb) anti-IgE MH25-1. Our results are in con trast with findings of other investigators who use pooled supernatants and demonstrated HRF-MN responsiveness with both allergic and nonalle rgic donors. We conclude that mononuclear cell supernatants derived fr om different mononuclear cell donors vary not only quantitatively but also qualitatively with respect to IgE-dependent histamine-releasing a ctivity.