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Cell deformability and the sequestration of neutrophils in the lungs during cigarette smoking

Neutrophil transit through the pulmonary circulation is delayed in comparison to the transit of erythrocytes. During inhalation of cigarette smoke, this delay or sequestration of neutrophils, which occurs in normal lungs, was found to be enhanced. This could facilitate neutrophil emigration into the airspace or activation of sequestered neutrophils could result in an elastase burden in the pulmonary vasculature. Hence, studies of the mechanism of the enhanced neutrophil sequestration during smoking would improve our knowledge and may lead to therapeutic interventions for smoke-induced lung diseases. The intravascular pulmonary sequestration of neutrophils is influenced by haemodynamic forces, the cell's ability to deform, and by an increase in adhesion between neutrophils and endothelial cells. This thesis has concentrated on the influence of cell deformability on neutrophil sequestration in the lungs and the effects of cigarette smoking. An <I>in vitro </I>measurement of cell deformability was compared to the <I>in vivo</I> kinetics of neutrophils in the lungs of man, to reveal a strong correlation between the first pass sequestration <I>in vivo</I> and <I>in vivo</I> cell deformability. Exposure of isolated neutrophils to the vapour phase of cigarette smoke <I>in vitro</I> caused a reduction in cell deformability. However, recovery of cell deformability was observed with time. The functional behaviour of smoke exposed neutrophils was also adversely affected. The mechanism for the reduction in cell deformability an exposure to cigarette smoke appeared to be due to the oxidant effect of smoke on the cell cytoskeleton. Moveover, in confirmation, a reduction in leucocyte deformability was observed in arterial but not venous blood, by measuring the filterability of diluted whole blood, following <I>in vivo </I>cigarette smoking.
Date January 1994
CreatorsDrost, Ellen Maria
PublisherUniversity of Edinburgh
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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