Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells
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) antibo...
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| Format: | Article |
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BioMed Central
2015
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| Online Access: | https://eprints.nottingham.ac.uk/30245/ |
| _version_ | 1848793950352048128 |
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| author | Gough, Kevin C. Maddison, Ben C. Shikotra, Aarti Moiseeva, Elena P. Yang, Weidong Jarvis, Shila Bradding, Peter |
| author_facet | Gough, Kevin C. Maddison, Ben C. Shikotra, Aarti Moiseeva, Elena P. Yang, Weidong Jarvis, Shila Bradding, Peter |
| author_sort | Gough, Kevin C. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:08:26Z |
| format | Article |
| id | nottingham-30245 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:08:26Z |
| publishDate | 2015 |
| publisher | BioMed Central |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-302452020-05-04T17:13:00Z https://eprints.nottingham.ac.uk/30245/ 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 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. BioMed Central 2015-07-15 Article PeerReviewed Gough, Kevin C., Maddison, Ben C., Shikotra, Aarti, Moiseeva, Elena P., Yang, Weidong, Jarvis, Shila and Bradding, Peter (2015) Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells. Respiratory Research, 16 . 86/1-86/11. ISSN 1465-9921 Mast cell Airway epithelium Airway smooth muscle Phage display ScFv Kit (CD117) http://www.respiratory-research.com/content/16/1/86 doi:10.1186/s12931-015-0245-z doi:10.1186/s12931-015-0245-z |
| spellingShingle | Mast cell Airway epithelium Airway smooth muscle Phage display ScFv Kit (CD117) Gough, Kevin C. Maddison, Ben C. Shikotra, Aarti Moiseeva, Elena P. Yang, Weidong Jarvis, Shila Bradding, Peter Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title | Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title_full | Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title_fullStr | Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title_full_unstemmed | Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title_short | Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| title_sort | evidence for a novel kit adhesion domain mediating human mast cell adhesion to structural airway cells |
| topic | Mast cell Airway epithelium Airway smooth muscle Phage display ScFv Kit (CD117) |
| url | https://eprints.nottingham.ac.uk/30245/ https://eprints.nottingham.ac.uk/30245/ https://eprints.nottingham.ac.uk/30245/ |