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Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells

Gough, Kevin C.; Maddison, Ben C.; Shikotra, Aarti; Moiseeva, Elena P.; Yang, Weidong; Jarvis, Shila; Bradding, Peter

Authors

KEVIN GOUGH kevin.gough@nottingham.ac.uk
Professor of Biochemistry and Pathology

Ben C. Maddison

Aarti Shikotra

Elena P. Moiseeva

Weidong Yang

Shila Jarvis

Peter Bradding



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 adhesion is not inhibited by function-blocking anti-Kit and anti-stem cell factor (SCF) antibodies. Our aim was to identify adhesion molecules expressed by human mast cells that mediate 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 mast cell 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 did not interfere with SCF-dependent Kit signalling.
Conclusion: Kit contributes to human mast cell adhesion to human airway epithelial cells and HASMCs, but may utilise a previously unidentified adhesion domain that lies outside the SCF 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.

Journal Article Type Article
Publication Date Jul 15, 2015
Journal Respiratory Research
Print ISSN 1465-9921
Electronic ISSN 1465-9921
Publisher Humana Press
Peer Reviewed Peer Reviewed
Volume 16
Article Number 86
APA6 Citation Gough, K. C., Maddison, B. C., Shikotra, A., Moiseeva, E. P., Yang, W., Jarvis, S., & Bradding, P. (2015). Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells. Respiratory Research, 16, doi:10.1186/s12931-015-0245-z
DOI https://doi.org/10.1186/s12931-015-0245-z
Keywords Mast cell, Airway epithelium, Airway smooth muscle, Phage display, ScFv, Kit (CD117)
Publisher URL http://www.respiratory-research.com/content/16/1/86
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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