REGULATION OF HISTAMINE-RELEASE FROM HUMAN BRONCHOALVEOLAR LAVAGE MAST-CELLS BY STEM-CELL FACTOR IN SEVERAL RESPIRATORY-DISEASES

We investigated the effects of stem cell factor (SCF) on histamine rel ease (HR) from human bronchoalveolar lavage (BAL) mast cells. BAL cell s were recovered from lavage performed in patients undergoing clinical bronchoscopy. SCF (0.02-20 ng/ml), which is by itself a poor secretag ogue (mean +/- SEM HR: 3.7+/-0.9%; n=27), strongly enhanced HR induced by anti-IgE in a concentration-related manner. Significant potentiati on began at 0.2 ng/ml (30+/-10%; p<0.05; n=12) and reached a plateau a t 2 ng/ml (40+/-10%; P<0.01 at 2 ng/ml and 45+/-10%; P< 0.01 at 20 ng/ ml; n=12). In contrast, SCF failed to enhance HR induced by calcium io nophore A23187. Among the BAL cell samples initially unresponsive to a nti-IgE (55% of samples), 36% (10/28) were converted to responders if the cells were shortly preincubated with SCF. In 25%, of samples (7/27 ), SCF (20 ng/ml) caused direct HR of 10+/-2.1%. The mast cells which released histamine when challenged with SCF also secreted higher level s of histamine in response to anti-IgE and calcium ionophore than thos e nonresponsive to SCF. While interleukin (IL)-3 and IL-5 (20 ng/ml) w ere unable to modulate immunologic HR, GM-CSF (20 ng/ml) produced sign ificant potentiation (P<0.05), which was, however, smaller than that o bserved with SCF. The rate of responders to anti-IgE in atopic asthma (47%) was greater than that in control (9%) and intrinsic asthma (10%) but not different from that in some other respiratory diseases such a s chronic bronchitis (44%) lung cancer (47%), or interstitial disease (68%). The potentiation of HR afforded by SCF did not differ significa ntly among the several disease groups. We conclude that, whatever the underlying respiratory disease, SCF selectively enhances IgE-mediated HR from human BAL mast cells. Furthermore, this cytokine is sometimes necessary to render mast cells able to release histamine in response t o anti-IgE.