PAF receptor antagonist modulates neutrophil responses with thermal injuryin vivo

The role of platelet-activating factor (PAF) in Ca2+ signaling and Ca2+-rel ated enhancement of reactive oxygen intermediate (ROI) generation in neutro phils of burn-injured rats was ascertained by evaluating the effect of trea tment of the rats with a PAF receptor antagonist. The treatment of rats wit h the antagonist also allowed us to evaluate the role of PAF in the priming of neutrophil ROI response with burn in vivo. A full skin thickness burn i njury was produced in anesthetized rats by exposing 30% of total body surfa ce area to 98 degreesC water for 10 s. Sham and burn rats were killed 1 day later, and their blood was collected to obtain neutrophils. Fluorescence-a ctivated cell sorter analysis was used to quantify ROI production by the ne utrophils. Cytosolic-free Call concentration ([Ca2+](i)) imaging technique was employed to measure neutrophil [Ca2+](i) in individual cells and microf luorometry for the assessment of [Ca2+](i) responses in suspensions of neut rophils. There was an overt enhancement of ROI generation by burn rat neutr ophils. ROI release was accompanied by a marked elevation of [Ca2+](i) sign aling. The treatment of rats with PAF receptor antagonist before burn preve nted the upregulation of both [Ca2+](i) and ROI generation in neutrophils. These studies indicate that enhanced ROI production in neutrophils in the e arly stages after burn injury results from a PAF-mediated priming of the [C a2+](i) signaling pathways in vivo.