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dc.contributor.advisor[non identifié]fr
dc.contributor.authorHaider, Waqar Yunusfr
dc.date.accessioned2014-05-16T12:48:54Z
dc.date.available2014-05-16T12:48:54Z
dc.date.created2010fr
dc.date.issued2010fr
dc.identifier.isbn9780494656280fr
dc.identifier.urihttp://savoirs.usherbrooke.ca/handle/11143/4024
dc.description.abstractNeutrophil degranulation involves a number of well-orchestrated structural and biochemical events. We have investigated the mechanism of intracellular signalling involved in neutrophil degranulation that was mediated by the high affinity leukotriene (LT)B[subscript 4] receptor, BLT1. The model systems used were consisted of Peripheral blood neutrophils as well as promyeloid PLB-985 cells, stably transfected with human BLT1 cDNA (PLB-BLT) or a substitution mutant (2L(304-305)/A) of the distal dileucine motif in helix VIII of BLT1, and differentiated into a neutrophil-like phenotype. The degranulation of these cells was measured in the presence and absence of factors that would affect the signaling pathway. The results show that Degranulation responses to LTB[subscript 4] were similar for differentiated PLB-BLT1 and neutrophils. However, the degranulation response of cells bearing the dileucine mutation in helix VIII of BLT1 was significantly reduced in response to LTB[subscript 4]. Pretreatment of differentiated PLB-BLT1 cells and neutrophils with Y-27632, a pharmacological inhibitor of p160-ROCK, the down-stream effector of the small GTPase RhoA, abrogated their degranulation in response to LTB[subscript 4]. The degranulation defect observed with the dileucine mutation was corrected by transient transfection of the cells bearing the mutation with a constitutively active form of RhoA. Taken together, our results suggest an essential role for the distal dileucine motif in helix VIII of BLT1 involving RhoA which allows normal neutrophil degranulation in response to LTB[subscript 4].fr
dc.language.isoengfr
dc.publisherUniversité de Sherbrookefr
dc.rights© Waqar Yunus Haiderfr
dc.subjectDegranulationfr
dc.subjectRhoA signalingfr
dc.subjectDistal dileucine motiffr
dc.subjectHelix VIIIfr
dc.subjectBLT1fr
dc.subjectNeutrophilfr
dc.titleThe role of the dileucine motif in Helix VIII of the BLT1 receptor and RhoA in neutrophil degranulationfr
dc.typeMémoirefr
tme.degree.disciplineImmunologiefr
tme.degree.grantorFaculté de médecine et des sciences de la santéfr
tme.degree.levelMaîtrisefr
tme.degree.nameM. Sc.fr


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