Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Background: Human lung mast cells (HLMCs) infiltrate the airway epithelium and airway smooth muscle (ASM) in asthmatic airways. The mechanism of HLMC adhesion to both cell types is only partly defined, and is not inhibited by function-blocking anti-Kit and anti-stem cell factor antibodies.Objective: To identify adhesion molecules expressed by human mast cells that mediate mast cell adhesion to human ASM cells (HASMCs) and human airway epithelial cells.Methods: We used phage-display to isolate single chain Fv (scFv) antibodies with adhesion-blocking properties from rabbits immunised with HLMC and HMC-1 membrane proteins.Results: Post-immune rabbit serum labelled HLMCs in flow cytometry and inhibited their adhesion to human BEAS-2B epithelial cells. Mast cell-specific scFvs were identified which labelled mast cells but not Jurkat cells by flow cytometry. Of these, one scFv (A1) consistently inhibited HMC-1 adhesion to HASMCs and BEAS-2B epithelial cells by about 30%. A1 immunoprecipitated Kit (CD117) from HMC-1 lysates and bound to a human Kit-expressing mouse mast cell line, but it did not interfere with stem cell factor-dependent Kit signalling.Conclusion: Kit contributes to human mast cell adhesion to human airway epithelial cells and HASMCs, but may involve a previously unidentified adhesion domain on Kit that lies outside the stem cell factor binding site. Targeting this adhesion pathway might offer a novel approach for the inhibition of mast cell interactions with structural airway cells, without detrimental effects on Kit signalling in other tissues.

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K. Gough, B. Maddison, A. Parmar, E. Moiseeva, W. Yang, S. Jarvis, P. Bradding (Leicestershire, Leicester, United Kingdom). Evidence for a novel kit adhesion domain mediating human mast cell adhesion to structural airway cells. Eur Respir J 2014; 44: Suppl. 58, 3850

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