Studies on the biochemical pharmacology of human dispersed skin mast cells
Studies on the biochemical pharmacology of human dispersed skin mast cells
The ability of mast cells to release histamine in response to IgE-dependent activation is well documented. Indirect evidence suggests that human skin mast cells may also release histamine in response to non-IgE-dependent stimuli. In this study, mast cells have been dispersed from human skin using collagenase and hyaluronidase. Dispersed skin mast cells release histamine in response to anti-IgE, calcium ionophore A23187, compound 48/80, poly-L-lysine, morphine, dynorphin, substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SOM). This histamine release is concentration-related and non-cytotoxic. Mast cells similarly dispersed from human lung, adenoids, tonsils, and colon, fail to release histamine in response to non-IgE-dependent stimuli. therefore, non-IgE-dependent histamine release from human skin mast cells represents functional heterogeneity between human mast cell sub-populations. IgE-dependent histamine release from human skin mast cells requires 5-7 minutes for completion, is wholly dependent on extracellular calcium, and is not inhibited in the presence of the substance P antagonist [D-Pro4,D-Trp7,9,10]SP4-11 (SPA). In contrast, non-IgE-dependent histamine release is complete within 20 seconds, is largely independent of extracellular calcium, and can be inhibited by SPA. This suggests IgE-dependent an non-IgE-dependent histamine release to occur via different mechanisms. The similar characteristics of histamine release induced by SP, compound 48/80, poly-L-lysine, morphine, VIP, and SOM, further suggests these stimuli to be acting via the same or similar activation sites. Studies with SP-related peptides show that the skin mast cell activation site for SP is not a tachykinin receptor of the NK1, NK2, or NK3 subtypes. In addition, both the basic N- and the lipophilic C-terminals of SP are required for full histamine releasing activity. IgE-dependent and non-IgE-dependent histamine release are unaffected by sodium cromoglycate, but inhibited by salbutamol or isobutylmethylxanthine. Terfenadine has a selective action, inhibiting only IgE-dependent activation. In conclusion, human dispersed skin mast cells release histamine in response to IgE-dependent and non-IgE-dependent activation. Although the physiological role of non-IgE-dependent activation is uncertain, the ability of neuropeptides to induce histamine release suggests an interaction between skin mast cells and nerves.
University of Southampton
1988
Lowman, Mark Andrew
(1988)
Studies on the biochemical pharmacology of human dispersed skin mast cells.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The ability of mast cells to release histamine in response to IgE-dependent activation is well documented. Indirect evidence suggests that human skin mast cells may also release histamine in response to non-IgE-dependent stimuli. In this study, mast cells have been dispersed from human skin using collagenase and hyaluronidase. Dispersed skin mast cells release histamine in response to anti-IgE, calcium ionophore A23187, compound 48/80, poly-L-lysine, morphine, dynorphin, substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SOM). This histamine release is concentration-related and non-cytotoxic. Mast cells similarly dispersed from human lung, adenoids, tonsils, and colon, fail to release histamine in response to non-IgE-dependent stimuli. therefore, non-IgE-dependent histamine release from human skin mast cells represents functional heterogeneity between human mast cell sub-populations. IgE-dependent histamine release from human skin mast cells requires 5-7 minutes for completion, is wholly dependent on extracellular calcium, and is not inhibited in the presence of the substance P antagonist [D-Pro4,D-Trp7,9,10]SP4-11 (SPA). In contrast, non-IgE-dependent histamine release is complete within 20 seconds, is largely independent of extracellular calcium, and can be inhibited by SPA. This suggests IgE-dependent an non-IgE-dependent histamine release to occur via different mechanisms. The similar characteristics of histamine release induced by SP, compound 48/80, poly-L-lysine, morphine, VIP, and SOM, further suggests these stimuli to be acting via the same or similar activation sites. Studies with SP-related peptides show that the skin mast cell activation site for SP is not a tachykinin receptor of the NK1, NK2, or NK3 subtypes. In addition, both the basic N- and the lipophilic C-terminals of SP are required for full histamine releasing activity. IgE-dependent and non-IgE-dependent histamine release are unaffected by sodium cromoglycate, but inhibited by salbutamol or isobutylmethylxanthine. Terfenadine has a selective action, inhibiting only IgE-dependent activation. In conclusion, human dispersed skin mast cells release histamine in response to IgE-dependent and non-IgE-dependent activation. Although the physiological role of non-IgE-dependent activation is uncertain, the ability of neuropeptides to induce histamine release suggests an interaction between skin mast cells and nerves.
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Published date: 1988
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Local EPrints ID: 460523
URI: http://eprints.soton.ac.uk/id/eprint/460523
PURE UUID: ea04888e-b15e-4f1d-8229-6d468340a145
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Date deposited: 04 Jul 2022 18:23
Last modified: 04 Jul 2022 18:23
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Author:
Mark Andrew Lowman
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