The effects of adhesion on human lung mast cells and basophils
The effects of adhesion on human lung mast cells and basophils
I was interested in the role of integrin signalling in mast cells and basophils and their role in the pathogenesis of asthma. It has been shown previously, that clustering of VLA-4 on the cell surface of human basophils results in histamine release but only from asthmatic donors. I have extended these studies to show that it is not only the asthmatic, but also the allergic status of these donors which is important for integrin dependent responses in human basophils. I have also shown that the model used to cluster the integrins was a good model for interactions with the matrix, as I achieved similar results to those seen following clustering of VLA-4 (CD29/CD49d) with the ligand for VLA-4, fibronectin. I have also shown that the results observed following ligation of VLA-4 on the basophils of asthmatics did not just reflect an increased 'releasability' of these cells, as responses to anti-IgE and spontaneous histamine release in allergic asthmatics were similar in non-allergic asthmatics, allergic non-asthmatics and non-allergic non-asthmatics. The results observed in the basophil have important implications in allergic asthma, where the altered environment of the asthmatic lung could have profound effects on the responses of basophils. I have outlined a mechanism by which basophils attracted into the tissue as part of the late phase inflammatory response may degranulate, even in the absence of allergen. I did not observe integrin or fibronectin induced histamine release from human lung mast cells, although I was unaware of the asthmatic or allergic status of the donors.
In order to exclude the possibility that the results observed following integrin clustering on human basophils were as a result of co-clustering of the high affinity IgE receptor, I investigated the signalling pathways involved in integrin and IgE dependent degranulation.
University of Southampton
1998
Goldring, Kirstin
(1998)
The effects of adhesion on human lung mast cells and basophils.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
I was interested in the role of integrin signalling in mast cells and basophils and their role in the pathogenesis of asthma. It has been shown previously, that clustering of VLA-4 on the cell surface of human basophils results in histamine release but only from asthmatic donors. I have extended these studies to show that it is not only the asthmatic, but also the allergic status of these donors which is important for integrin dependent responses in human basophils. I have also shown that the model used to cluster the integrins was a good model for interactions with the matrix, as I achieved similar results to those seen following clustering of VLA-4 (CD29/CD49d) with the ligand for VLA-4, fibronectin. I have also shown that the results observed following ligation of VLA-4 on the basophils of asthmatics did not just reflect an increased 'releasability' of these cells, as responses to anti-IgE and spontaneous histamine release in allergic asthmatics were similar in non-allergic asthmatics, allergic non-asthmatics and non-allergic non-asthmatics. The results observed in the basophil have important implications in allergic asthma, where the altered environment of the asthmatic lung could have profound effects on the responses of basophils. I have outlined a mechanism by which basophils attracted into the tissue as part of the late phase inflammatory response may degranulate, even in the absence of allergen. I did not observe integrin or fibronectin induced histamine release from human lung mast cells, although I was unaware of the asthmatic or allergic status of the donors.
In order to exclude the possibility that the results observed following integrin clustering on human basophils were as a result of co-clustering of the high affinity IgE receptor, I investigated the signalling pathways involved in integrin and IgE dependent degranulation.
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Published date: 1998
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Local EPrints ID: 463160
URI: http://eprints.soton.ac.uk/id/eprint/463160
PURE UUID: aa9ed9f3-c0a1-4d52-97d7-537ff8c4bcb2
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Date deposited: 04 Jul 2022 20:46
Last modified: 04 Jul 2022 20:46
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Author:
Kirstin Goldring
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