Intravascular anti-IgE challenge in perfused lungs: mediator release and vascular pressor response.
Intravascular application of goat anti-rabbit immunoglobulin E (IgE) was used to stimulate parenchymal mast cells in situ in perfused rabbit lungs. Sustained pulmonary arterial pressure rise was evoked in the absence of lung vascular permeability increase and lung edema formation. Early prostaglandin (PG) D2 and histamine release into the perfusate was documented, accompanied by more sustained liberation of cysteinyl leukotrienes (LT), LTB4, and PGI2. The quantities of these inflammatory mediators displayed the following order: histamine greater than cysteinyl-LT greater than PGI2 greater than LTB4 greater than PGD2. Pressor response and inflammatory mediator release revealed corresponding bell-shaped dose dependencies. Cyclooxygenase inhibition (acetylsalicylic acid) suppressed prostanoid generation, increased LT release, and did not substantially affect pressor response and histamine liberation. BW755 C, a cyclo- and lipoxygenase inhibitor, blocked the release of cysteinyl-LT and markedly reduced the liberation of the other inflammatory mediators as well as the pressor response. The H1-antagonist clemastine caused a moderate reduction of the anti-IgE-provoked pressure rise. We conclude that intravascular anti-IgE challenge in intact lungs provokes the release of an inflammatory mediator profile compatible with in situ lung parenchymal mast cell activation. Pulmonary hypertension represents the predominant vascular response, presumably mediated by cysteinyl-LT and, to a minor extent, histamine liberation.
Walmrath
D
D
Department of Internal Medicine, Justus-Leibig University, Giessen, Federal Republic of Germany.
Schneider
U
U
Kreusler
B
B
Grimminger
F
F
Ennis
M
M
Seeger
W
W
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D001794:Blood Pressure / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006636:Histamine Release; D007073:Immunoglobulin E; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000276:immunology* / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D010477:Perfusion; D015230:Prostaglandin D2 / Q000378:metabolism; D011817:Rabbits
D000888:Antibodies, Anti-Idiotypic; D007073:Immunoglobulin E; D011464:Epoprostenol; D015230:Prostaglandin D2