Pulmonary and neutrophil responses to priming effects of platelet-activating factor in pigs.
OBJECTIVE
To investigate whether platelet-activating factor (PAF) primes the porcine pulmonary response to lipopolysaccharide (LPS), and what effect PAF priming has on porcine neutrophil superoxide (SO) release.


METHODS
8- to 10-week old pigs.


METHODS
After pigs were anesthetized with sodium pentobarbital and instrumented for standard cardiopulmonary hemodynamic measurements, they were randomly assigned to receive PAF (0.1 ng/kg of body weight/min, 0 to 2 hours) plus saline solution (2 to 6 hours), saline solution (0 to 2 hours) plus LPS (0.25 microgram/kg/h, 2 to 6 hours), or PAF plus LPS. Cardiopulmonary variables were measured throughout the study. Neutrophils were isolated from saline- or PAF-treated pigs at 0 (baseline) and 2 hours, and the effect of in vivo PAF exposure on ex vivo phorbol myristate acetate (PMA)-induced SO release was measured. Additionally, neutrophils isolated from immune-naive pigs were primed in vitro for 10 minutes with 10 microM PAF, and PMA-induced SO release was measured.


RESULTS
PAF infusion significantly enhanced the increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and hypoxemia associated with LPS administration. The infusion increased ex vivo neutrophil SO release, and in vitro PAF exposure primed neutrophils for enhanced SO release that was inhibited by pretreatment of cells with indomethacin.


CONCLUSIONS
PAF primes the porcine pulmonary system for the response to LPS. It primes porcine neutrophils in vivo and in vitro for PMA-induced SO release, and in vitro priming is mediated by cyclooxygenase products of arachidonic acid metabolism.


CONCLUSIONS
PAF may modulate the porcine inflammatory response by acting as a priming agent, making pigs more responsive to the negative effects of bacterial LPS.
Kruse-Elliott
K T
KT
Department of Surgical Sciences, University of Wisconsin, Madison 53706, USA.
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001784:Blood Gas Analysis / Q000379:methods / Q000662:veterinary; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002273:Carcinogens / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011897:Random Allocation; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000098:blood supply / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013552:Swine / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013481:Superoxides; D016718:Arachidonic Acid; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin