Introduction Constitutive and IgE-dependent secretion of histamine from human lung mast cells (HLMC) is suppressed by direct contact with the BEAS-2B bronchial epithelial cell line, but not conditioned epithelial cell media. This suggests that direct contact or a low concentration/labile secreted factor is involved. We explored this relationship further using a Transwell co-culture system of HLMC with BEAS-2B monolayers or air liquid interface primary bronchial epithelial cultures (ALI) derived from asthmatic and healthy subjects.
Methods ALI and BEAS-2B were grown on Transwell membranes. IgE-sensitised HLMC were then cultured i) on the luminal surface of a BEAS-2B monolayer, ii) separated from the BEAS-2B basal surface by a Transwell membrane, or iii) on the well bottom with BEAS-2B and ALI sitting on the Transwell insert. Cells were co-cultured for 16 h, media removed, and HLMC stimulated with anti-IgE for 30 min. Parallel controls without epithelial cells were performed. Histamine concentrations were determined by radioenzymic assay.
Results BEAS-2B (n=3): Compared to no epithelium control, constitutive histamine secretion from HLMC in direct contact with BEAS-2B was suppressed by a mean (±SEM) 57±15% (p=0.04), and by 55±9% when separated by Transwells (p=0.02). IgE-dependent secretion was suppressed by 79±8% (p=0.04) from HLMC in direct contact with BEAS-2B and by 88±7% (p=0.03) when separated by Transwells, compared to control. ALI-culture (n=6 healthy, 6 asthmatic): Compared to control, healthy ALI suppressed constitutive HLMC histamine release by 39±5% (p=0.01), but asthmatic ALI did not (mean 19±11% suppression, p=0.07). There was a significant difference between healthy compared to asthmatic ALI (p=0.01). Healthy and asthmatic ALI suppressed IgE-dependent histamine release by 55±4%, p=0.001 and 48±1%, p=0.001, respectively.
Conclusions BEAS-2B and healthy airway epithelial cells suppress constitutive and IgE-dependent HLMC histamine secretion when separated by Transwell membranes. Asthmatic ALI cultures do not suppress constitutive HLMC histamine secretion, but do suppress IgE-dependent secretion. These results suggest that the normal regulation of this process is by a secreted, probably labile factor(s), which may be partially deficient in asthma. Isolation and manipulation of this factor may have interesting therapeutic potential.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.