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Linking airways inflammation and remodelling
S33 Suppression of constitutive and stimulated secretion of histamine from human lung mast cells by a secreted factor from lung epithelial cells
  1. N Martin,
  2. G K Arthur,
  3. W Y H Wan,
  4. L Woodman,
  5. C E Brightling,
  6. I D Pavord,
  7. P Bradding
  1. Institute for Lung Health, Glenfield Hospital, Leicester, UK

Abstract

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.

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