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 release (HR) from human bronchoalveolar lavage (BAL) mast cells. BAL cells were recovered from lavage performed in patients undergoing clinical bronchoscopy. SCF (0.02-20 ng/ml), which is by itself a poor secretagogue (mean ± SEM HR : 3.7 ± 0.9% ; n = 27), strongly enhanced HR induced by anti-IgE in a concentration-related manner. Significant potentiation began at 0.2 ng/ml (30 ± 10% ; p<0.05 ; n = 12) and reached a plateau at 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 ionophore A23187. Among the BAL cell samples initially unresponsive to anti-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 levels of histamine in response to anti-IgE and calcium ionophore than those nonresponsive to SCF. While interleukin (IL)-3 and IL-5 (20 ng/ml) were unable to modulate immunologic HR, GM-CSF (20 ng/ml) produced significant potentiation (P<0.05), which was, however, smaller than that observed 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 as chronic bronchitis (44%), lung cancer (47%), or interstitial disease (68%). The potentiation of HR afforded by SCF did not differ significantly 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 to anti-IgE.