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Effect of neutrophil priming and de-priming on neutrophil retention in the lung. (360G-Wellcome-077940_Z_05_Z)

Neutrophils become 'primed' after exposure to inflammatory mediators and this greatly enhances their subsequent secretory activity. Priming also alters neutrophil shape/deformability, integrin expression and longevity and hence has a profound affect on their rheological, adhesive and survival properties. Priming is a prerequisite for neutrophil-mediated tissue injury and plays a fundamental role in the pathogenesis of ARDS. Since priming is reversible, I will test whether the pulmonary capillary bed and/or spleen can trap and de-prime systemically-primed neutrophils before releasing them back into the circulation, and whether failure of this function results in neutrophil-mediated lung injury.Specifically, I will address:(i) What is the bio-distribution, preferential disposal site and circulating half-life of primed versus un-primed neutrophils? This will be addressed using 99mTc and 111In-labelled primed/un-primed neutrophils in healthy volunteers.(ii) Can pulmonary capillaries or the spleen retain circulating primed neutrophils, de-prime them and return them to the circulation? I will determine the capacity for neutrophils primed in vivo to de-prime ex-vivo and use flow-based techniques to track the intravascular fate of permanently or transiently primed 111In-labelled cells.(iii) What is the effect of lung vascular (ARDS) and airspace (pneumonia) inflammation on transpulmonary primed neutrophil gradients and does neutrophil transit time and pulmonary retention fraction predict the evolution of ARDS.

£235,646

06 Dec 2005

Grant details
Amount Awarded 235646
Applicant Surname Summers
Approval Committee Clinical Interview Committee
Award Date 2005-12-06T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Training Fellowship
Internal ID 077940/Z/05/Z
Lead Applicant Dr Charlotte Summers
Planned Dates: End Date 2009-05-31T00:00:00+00:00
Planned Dates: Start Date 2006-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Edwin Chilvers
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