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Some studies on the hyperosmolar stimulation of mast cells from the rodent and human

Makhdum, Arshad Mohammed; (1997) Some studies on the hyperosmolar stimulation of mast cells from the rodent and human. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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In many asthmatic subjects, vigorous exercise leads to a pronounced bronchoconstriction, a phenomenon termed exercise induced asthma (EIA). The cause of this condition is unknown but it has been suggested that respiratory water loss may increase the osmolarity of the pericilliary fluid, thereby inducing mast cell activation. This effect may be mimicked in vitro by the use of hyperosmolar buffers and we thus first characterised the effect of such buffers on isolated mast cells and basophils from different sources. Hyperosmolar buffers produced by the addition of D-Mannitol (0.1-1.0 M) induced histamine release from mast cells from dispersed human lung (DL), guinea pig lung (GPL), bronchoalveolar lavage (BAL), the rat peritoneal cavity (RPMC) and human basophil leucocytes (HB). The maximal releases were ca 60 % (HB and RPMC), 40 % (BAL) and 15 % (GPL and DL) respectively. Excluding DL mast cells, this release was non-cytotoxic and was inhibited by metabolic blockers. In all cases, however, release was diminished at extremes of temperature. The process was relatively fast in all cases in comparison with HB, where the release required 20-60 min for completion. DL, BAL and GPL mast cells all required extracellular calcium for the release process, unlike RPMC and HB, which were only partially calcium- dependent. The interaction between mannitol and anti-lgE was synergistic in HB, but additive in both purified and non-purified RPMC. A similar weak interaction occurred between ionophore A23187 and mannitol in both RPMC and HB. Mannitol (0.2-1.0 M), in addition to the secretion of preformed mediators, also induced the de novo synthesis of prostaglandin D2 (PGD2) in a dose related manner from purified RPMC. Similarly, the PGD2 secreted due to interaction between anti-lgE and mannitol was also studied and its correlation with histamine release noted. The effect of anti-allergic compounds on the inhibition of histamine release in RPMC and HB was then studied. Anti-asthmatic compounds were powerful inhibitors in both cell types. ß-agonists were weak inhibitors, as were diuretics. The histamine release in both RPMC and HB was potentiated by drugs that increase intracellular cyclic adenosine monophosphate (cAMP). In contrast, all of these compounds produced a moderate inhibition (ca 30-40 %) of histamine release from BAL mast cells. In total, this study affords an insight into possible mechanistic differences between hyperosmolar and IgE-directed stimulation of mast cells and basophil leucocytes.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Some studies on the hyperosmolar stimulation of mast cells from the rodent and human
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Hyperosmolar stimulation; Mast cells
URI: https://discovery.ucl.ac.uk/id/eprint/10100682
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