Acute microvascular effects of PAF-acether, as studied by intravital microscopy

Application of PAF-acether (platelet-activating factor) (final concentration 1-20 nM) to the microcirculation of the hamster cheek pouch resulted in dose-dependent vasoconstriction and an increase in macromolecular permeability, as assessed by leakage of intravascular fluorescein-labelled dextran (Mw 150 000). An increase in adhering leukocytes in venules was only seen with 20 nM PAF-acether. Animals made neutropenic by treatment with antineutrophil serum raised in rabbits showed a reduced leakage response to 20 nM PAF-acether, whereas the leakage induced with 5 nM PAF-acether was unaffected. This indicates that the increase in vascular permeability induced by PAF-acether occurs both as a presumably direct effect independent of polymorphonuclear leukocytes (PMNL), and via an indirect PMNL-dependent mechanism. Intravenous administration of PAF-acether (10 micrograms/kg body weight) to hamsters resulted in rapid and transient thrombocytopenia and leukopenia whereas 1 microgram/kg only affected the leukocytes. These potent microvascular effects of PAF-acether support its proposed role as a mediator of allergic and inflammatory reactions.