Detection of Histamine Release Inhibitory Factor- and Histamine Releasing Factor-like Activities in Bronchoalveolar Lavage Fluids

Abstract

Histamine releasing factors (HRF) are a group of cytokines that cause degranulation of basophils and mast cells. Recently we have described a histamine release inhibitory factor (HRIF) that inhibits HRF-induced histamine release from basophils and mast cells. The objective of this study was to investigate the presence of these cytokines in bronchoalveolar lavage (BAL) fluid from normal subjects. We found that BAL fluids from 12 to 17 volunteers contained a dialyzable (molecular weight cutoff 3500) factor that inhibited basophil histamine release by HRF, anti-IgE, concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, BAL fluids from 83% of the tested donors contained a nondialyzable inhibitor that blocked HRF-induced histamine release from basophils. The molecular weight of this inhibitor was estimated to be 20 to 30 and 8 to 10 kD by Sephadex G-50 chromatography and TSK 2000 size-exclusion HPLC. None of the unconcentrated BAL fluids showed any HRF activity on initial screening using basophils from allergic subjects. However, when the BAL fluids were concentrated, all BAL samples that were tested (N = 10) demonstrated significant HRF activity. The molecular weight of BAL HRF has been estimated to be in the range of 15 to 25 kD by size-exclusion HPLC, similar to the HRF synthesized by mononuclear cells. Thus we have demonstrated the presence of both HRF and HRIF in the BAL fluids. We speculate that these cytokines may be involved in the local regulation of basophil and mast cell activation.