PAF receptor antagonist modulates neutrophil responses with thermal injury in vivo.
The role of platelet-activating factor (PAF) in Ca(2+) signaling and Ca(2+)-related enhancement of reactive oxygen intermediate (ROI) generation in neutrophils of burn-injured rats was ascertained by evaluating the effect of treatment of the rats with a PAF receptor antagonist. The treatment of rats with 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 injury was produced in anesthetized rats by exposing 30% of total body surface area to 98 degrees C water for 10 s. Sham and burn rats were killed 1 day later, and their blood was collected to obtain neutrophils. Fluorescence-activated cell sorter analysis was used to quantify ROI production by the neutrophils. Cytosolic-free Ca(2+) concentration ([Ca(2+)](i)) imaging technique was employed to measure neutrophil [Ca(2+)](i) in individual cells and microfluorometry for the assessment of [Ca(2+)](i) responses in suspensions of neutrophils. There was an overt enhancement of ROI generation by burn rat neutrophils. ROI release was accompanied by a marked elevation of [Ca(2+)](i) signaling. The treatment of rats with PAF receptor antagonist before burn prevented the upregulation of both [Ca(2+)](i) and ROI generation in neutrophils. These studies indicate that enhanced ROI production in neutrophils in the early stages after burn injury results from a PAF-mediated priming of the [Ca(2+)](i) signaling pathways in vivo.
Fazal
N
N
Trauma/Critical Care Labs, Department of Surgery, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Al-Ghoul
W M
WM
Choudhry
M A
MA
Sayeed
M M
MM
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium