Effect of platelet activating factor on formation and composition of airway fluid in the guinea-pig trachea

Abstract

1. We studied the effect of platelet activating factor (PAF) on leakage of albumin, and secretion of fucose (a marker for mucus glycoprotein) and protein into the tracheal lumen of the guinea-pig isolated in situ, and on bioelectric properties and fluxes of mannitol in vitro. We also studied the effect of PAF on mucus secretion in human bronchi in vitro. 2. In guinea-pig, intravenous PAF markedly increased the luminal concentration of protein but did not significantly increase fucose concentrations. Increased albumin leakage (274% above controls at a dose of 50 ng/kg PAF) was associated with the increased luminal content of protein (248% above controls at the same dose of PAF). 3. Leakage of albumin was maximal 10 min after PAF, was significantly reduced by 20 min and had returned to baseline by 30 min. This pattern of leakage could be repeated with successive administrations of PAF. 4. PAF induced small but significant biphasic changes in bioelectric properties in vitro. The initial response was rapid in onset and characterized by maximal increases in short-circuit current (Isc) of 6.5% above controls at 7.5 min and in conductance (G) of 7% at 20 min. Both responses were blocked by the PAF receptor antagonist WEB 2086. Amiloride blocked the increase in Isc. Permeability of the tissue to mannitol (Pmann) was unaltered. The delayed response was characterized by maximal increases in Isc and G of 10% above controls at 60-90 min which were not significantly affected by WEB 2086 or amiloride. Pmann was increased by 38% at 90 min. 5. PAF increased fucose secretion in human bronchi in vitro. 6. Lyso-PAF in vitro caused changes similar to those induced by PAF on bioelectric properties and mucus secretion, but had no significant effects in vivo. 7. Light microscopy showed no evidence of epithelial disruption in animals given intravenous PAF at a dose causing significant albumin transudation. 8. We conclude that PAF increases the protein content of guinea-pig tracheal fluid principally by inducing plasma leakage rather than mucus secretion and that the small changes in ion transport and epithelial conductance may reduce the tendency to epithelial disruption during plasma leakage.