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We collected individual pools of nasal washings (NWs) from 15 allergic and 15 nonallergic subjects to determine histamine-releasing factor (HRF) activity and to ascertain the relationship of these cytokines with atopic status, basophil releasability, and cell membrane-bound IgE. NWs were concentrated, dialyzed, and assayed with basophils from a single donor. Samples from 12 of 15 allergic subjects and from all the nonallergic subjects revealed greater than or equal to 15% histamine release (HR), 33.5% +/- 21.3% (mean +/- SD) and 38.6% +/- 19.6%, respectively (p greater than 0.05). When we assayed the same samples with autologous basophils, the allergic group demonstrated higher HR than the nonallergic group (31.9% +/- 19.7% versus 4.8% +/- 4.3%; p less than 0.001). A standard lot of mononuclear cell-derived HRFs was also screened with basophils from both groups. Means for HR from basophils of allergic and nonallergic subjects were 51.9% +/- 16.7% versus 26.3% +/- 8.2%, respectively (p less than 0.001). Pretreatment of basophils with lactic acid led to abrogation of sensitivity to HRF. Acid-stripped cells incubated with sera from patients with asthma regained their capacity to release histamine. We found that HRF activity can be detected in NWs of most donors, and there is no difference among allergic and nonallergic subjects. Our results suggest that the capacity of these cytokines to induce HR depends on several factors: atopic status, basophil releasability, and membrane-bound IgE.

Certain species of histamine-releasing factor (HRF) have been demonstrated to distinguish a select group of allergic patients from healthy subjects. An IgE-dependent mechanism of action has been suggested. The donor and IgE dependency of HRF produced by peripheral blood mononuclear cells (PBMCs) has not been clearly demonstrated. In this study, we have compared the response of basophils from normal subjects versus allergic patients with and without asthma. In addition, we have addressed the IgE dependency of HRF recovered from cultures of PBMCs, T cells, B cells, macrophages, and bronchoalveolar lavage fluid. We have demonstrated that basophils from allergic as well as normal subjects respond to PBMC-HRF. The response of basophils from allergic patients with asthma is significantly increased. This heightened response to HRF does not correlate with the severity of disease as assessed by baseline spirometry, medication, and skin test scores. Stripping of the membrane-bound IgE by incubating basophils with lactic acid causes a significant loss of sensitivity to HRF generated by PBMCs, T cells, B cells, and macrophages, as well as to HRF recovered from bronchoalveolar fluid. The loss of response can be restored by sera from patients with asthma but not from normal subjects or by myeloma IgE. In addition, poorly responsive basophils from normal subjects can be rendered sensitive by incubating with sera from patients with asthma. The capacity of a given serum from a patient with asthma to restore the response to HRF is not correlated with the total concentration of IgE in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)