Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells..pdf (2.22 MB)
Download file

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

Download (2.22 MB)
journal contribution
posted on 30.07.2015, 09:13 by K. C. Gough, B. C. Maddison, Aarti Shikotra, Elena P. Moiseeva, Weidong Yang, Shila Jarvis, Peter Bradding
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.

History

Citation

Respiratory Research 2015, 16, 86

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Respiratory Research 2015

Publisher

BioMed Central

issn

1465-9921

eissn

1465-993X

Acceptance date

01/07/2015

Copyright date

2015

Available date

30/07/2015

Publisher version

http://www.respiratory-research.com/content/16/1/86

Language

en

Usage metrics

Categories

Licence

Exports