Enhancement of pulmonary inflammation by PGE2: evidence for a vasodilator effect.
We explored the potential proinflammatory effect of prostaglandins of the E series (PGE's) in a rabbit model of acute pulmonary inflammation. The instillation of fragments of the fifth component of complement (C5f) into the lung resulted in a localized area of inflammation, the extent of which was quantified by the total number of neutrophils and protein recoverable by bronchoalveolar lavage (BAL). Utilizing 111In-labeled neutrophils and serial scintigraphy, neutrophil localization in the area of inflammation was detected as early as 20 min after C5f instillation and reached a maximum between 2 and 4 h. The simultaneous intrabronchial administration of 100 micrograms of PGE2 resulted in a twofold increase in the accumulation of neutrophils in the area of inflammation as determined scintigraphically, a fivefold increase in BAL neutrophils, and a threefold increase in BAL protein. A proinflammatory effect on lavage constituents was also seen with the intravenous administration of PGE2 (100 ng.kg-1.min-1) and PGE1 (50 ng.kg-1.min-1) as well as in animals pretreated with a PGH synthase inhibitor, meclofenamate, and a thromboxane synthase inhibitor, dazmegrel. The effect of intrabronchial PGE2 to potentiate the inflammatory response was attenuated by the intravenous administration of a vasoconstrictor (angiotensin II) and mimicked by a vasodilator (nitroprusside), suggesting an effect of vasodilation per se. Using radiolabeled microspheres, it was determined that in response to the C5f alone, there was a 50% decrease in local blood flow to the area of inflammation, a pattern different from that seen in the systemic circulation. This decrease was prevented by the concomitant administration of PGE2 or nitroprusside. We conclude that vasodilation induced by PGE2 is associated with enhancement of pulmonary inflammation.
Downey
G P
GP
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver 80206.
Gumbay
R S
RS
Doherty
D E
DE
LaBrecque
J F
JF
Henson
J E
JE
Henson
P M
PM
Worthen
G S
GS
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003182:Complement C5; D015232:Dinoprostone; D008168:Lung / Q000098:blood supply*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D011458:Prostaglandins E / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D003182:Complement C5; D011458:Prostaglandins E; D015232:Dinoprostone