Journal of Applied Physiology, Vol 66, Issue 4 1860-1866, Copyright © 1989 by American Physiological Society
Evidence for platelet-activating factor secretion during immune activation in dogs
N. M. Munoz, N. P. Stimler-Gerard, M. M. Mack, C. Tutins, J. S. Blake, E. Kelly, T. M. Murphy and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637.
To elucidate the potential physiological significance of
platelet-activating factor (PAF) in acute bronchoconstriction, we studied
the effect of Ascaris suum antigen on the tachyphylactic response to PAF in
15 natively allergic mongrel dogs in vivo. Active bronchial tension was
measured isometrically, and mediator secretion was measured as the
arteriovenous difference (AVd) in plasma concentration across the lungs.
Administration of PAF into the bronchial artery caused dose-related
contraction in five control dogs (maximal active tension = 11.8 +/- 1.68
g/cm) that paralleled the increase in the AVd for serotonin (4,188 +/- 175
pg/ml) but not histamine (maximal AVd less than 6.0 ng/ml). The response to
PAF was highly tachyphylactic. In contrast to PAF, 1:10 concentration of
intra-arterial antigen caused substantial release of histamine (AVd = 308
+/- 57.1 ng/ml; P less than 0.001 vs. PAF). Diminished responsiveness
(2-log shift in threshold and maximal contraction; P less than 0.001) to
PAF was demonstrated in five dogs after 1:10 antigen, compatible with
endogenous release of PAF during prior immune challenge in the same
animals. Administration of Ascaris antigen caused a leftward shift in the
dose-response curve to serotonin and only mild tachyphylaxis to the maximal
response to histamine. Our data are compatible with physiological
participation of PAF in eliciting bronchial smooth muscle contraction
during the acute phase of immune activation caused by A. suum antigen.
