Interactions between extracellular Hsp72 and blood cells

Hdl Handle:
http://hdl.handle.net/10034/277691
Title:
Interactions between extracellular Hsp72 and blood cells
Authors:
Williams, Helen
Abstract:
In recent years, compelling evidence has accumulated suggesting heat shock proteins (HSPs) which are generally believed to be localised and functioning mainly within eukaryotic cells as cyto-protective molecular chaperones, are also localised in the extracellular milieu. Depending on their localisation, on the cell surface (membrance-bound or embedded), or in the peripheral circulation, extracellular HSPs may induce apoptotic cell death, or in contrast protect cells from cell damage and/or cell death when exposed to cellular stress, or may even elicit a stimulatory effect on the innate immune response including cell activiation and cytokine secretion. Hence, the localisation of intracellular and extracellular HSPs appears to be critical in determining their roles in terms of stimulating cell death, cyto-protection, or immune activiation under normal physiological conditions and following exposure to stress stimuli. This thesis describes the intracellular expression, up-regulation, and cell surface localisation of endogenous HSPs: HSP27, Hsp60, Hsp72 and Hsp90 by flow cytometry, florescence microscopy and Western blotting, under control conditions and in response to environmental stress using in vitro and ex vivo models with the intention of determining their physiological roles. The ability of extracellularly administered HSPs (Hsp70 and Hsp72) to protect cultured U937 cells in vitro or peripheral primary human leukogytes or erythrocytes ex vivo from various stress stimuli was demonstrated and was found to be dependent on surface binding and/or internalisation via scavenger receptors (SRs) or phosphatidylserine (PS), which could be blocked by receptor specific ligands. Extracellular HSPs were also shown to be able to stimulate an immune response through the induction of U937 monocyte differentiation into macrophages as evidenced through the up-regulation of the surface receptors: CD36, SR-A1 and CD91 analysed by flow cytometry. These proteins were able to stimulate TNF-x and IL-10 production and secretion by U937 macrophages, shown by ELISA, and chemotatic properties were demonstrated using Boyden chambers. The cyto-protective and immune regulatory effects of extracellular HSPs have potential therapeutic value as treatments in a wide variety of clinical situations.
Advisors:
Williams, John H. H.; Ireland, H. Elyse
Citation:
Williams, H., Ireland, H. E., & Williams, J. H. H. (2010). Hsp72 activates macrophage differentiation and is a chemoattractant for leukocytes. Inflammation Research, 59 (supplement 1), A211
Publisher:
University of Liverpool (University of Chester)
Publication Date:
Dec-2010
URI:
http://hdl.handle.net/10034/277691
Type:
Thesis or dissertation
Language:
en
Description:
Not to be added to EThOS
Sponsors:
Gladstone bursary from the University of Chester
Appears in Collections:
Theses

Full metadata record

DC FieldValue Language
dc.contributor.advisorWilliams, John H. H.en_GB
dc.contributor.advisorIreland, H. Elyseen_GB
dc.contributor.authorWilliams, Helenen_GB
dc.date.accessioned2013-04-02T10:56:03Zen
dc.date.available2013-04-02T10:56:03Zen
dc.date.issued2010-12en
dc.identifieruk.bl.ethos.539535en
dc.identifier.citationWilliams, H., Ireland, H. E., & Williams, J. H. H. (2010). Hsp72 activates macrophage differentiation and is a chemoattractant for leukocytes. Inflammation Research, 59 (supplement 1), A211en_GB
dc.identifier.urihttp://hdl.handle.net/10034/277691en
dc.descriptionNot to be added to EThOSen_GB
dc.description.abstractIn recent years, compelling evidence has accumulated suggesting heat shock proteins (HSPs) which are generally believed to be localised and functioning mainly within eukaryotic cells as cyto-protective molecular chaperones, are also localised in the extracellular milieu. Depending on their localisation, on the cell surface (membrance-bound or embedded), or in the peripheral circulation, extracellular HSPs may induce apoptotic cell death, or in contrast protect cells from cell damage and/or cell death when exposed to cellular stress, or may even elicit a stimulatory effect on the innate immune response including cell activiation and cytokine secretion. Hence, the localisation of intracellular and extracellular HSPs appears to be critical in determining their roles in terms of stimulating cell death, cyto-protection, or immune activiation under normal physiological conditions and following exposure to stress stimuli. This thesis describes the intracellular expression, up-regulation, and cell surface localisation of endogenous HSPs: HSP27, Hsp60, Hsp72 and Hsp90 by flow cytometry, florescence microscopy and Western blotting, under control conditions and in response to environmental stress using in vitro and ex vivo models with the intention of determining their physiological roles. The ability of extracellularly administered HSPs (Hsp70 and Hsp72) to protect cultured U937 cells in vitro or peripheral primary human leukogytes or erythrocytes ex vivo from various stress stimuli was demonstrated and was found to be dependent on surface binding and/or internalisation via scavenger receptors (SRs) or phosphatidylserine (PS), which could be blocked by receptor specific ligands. Extracellular HSPs were also shown to be able to stimulate an immune response through the induction of U937 monocyte differentiation into macrophages as evidenced through the up-regulation of the surface receptors: CD36, SR-A1 and CD91 analysed by flow cytometry. These proteins were able to stimulate TNF-x and IL-10 production and secretion by U937 macrophages, shown by ELISA, and chemotatic properties were demonstrated using Boyden chambers. The cyto-protective and immune regulatory effects of extracellular HSPs have potential therapeutic value as treatments in a wide variety of clinical situations.en_GB
dc.description.sponsorshipGladstone bursary from the University of Chesteren_GB
dc.language.isoenen
dc.publisherUniversity of Liverpool (University of Chester)en
dc.subjectHsp72en_GB
dc.subjectheat shock proteinsen_GB
dc.titleInteractions between extracellular Hsp72 and blood cellsen_GB
dc.typeThesis or dissertationen
dc.type.qualificationnamePhDen
dc.type.qualificationlevelDoctoralen
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