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Platelet-activating factor-induced microvascular dysfunction: role of adherent leukocytes
P Kubes1, M Suzuki, D N Granger
1Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Abstract:
Platelet-activating factor (PAF) has been implicated in the pathogenesis of intestinal mucosal injury associated with endotoxemia, inflammation, allergic reactions, and ischemia-reperfusion. Although it is generally held that PAF initiates mucosal injury by enhancing transcapillary fluid and protein exchange, the effects of PAF on the intestinal microvasculature have not been defined to date. In this study we examined the influence of local intrarterial infusions of PAF (4, 20, and 40 ng/min) on intestinal transcapillary, lymphatic, and transmucosal water and protein fluxes. All of these parameters were increased by each of the concentrations of PAF. PAF caused a large rise in venous hematocrit without a corresponding increase in venous plasma protein concentration and a 14- to 37-fold increase in vascular protein flux. Local intra-arterial infusion of PAF promoted leukocyte adherence to mesenteric venular endothelium, a process that is inhibited by the monoclonal antibody, MoAb IB4. PAF-induced increments in intestinal lymph flow, venous hematocrit, and vascular protein flux were greatly attenuated in animals treated with MoAb IB4. The results of this study indicate that PAF promotes the filtration of fluid and protein across intestinal capillaries. These microvascular effects of PAF are mediated, in part, by adherent leukocytes.
Insights
Platelet-activating factor (PAF) increases fluid and protein leakage in the gut microvasculature. This process, involving leukocyte adhesion, contributes to intestinal injury during inflammation and ischemia.
Area of Science:
- Gastroenterology
- Microcirculation Physiology
- Immunology
Background:
- Platelet-activating factor (PAF) is linked to intestinal injury in conditions like endotoxemia and ischemia-reperfusion.
- The precise effects of PAF on intestinal microvascular exchange remain incompletely understood.
Purpose of the Study:
- To investigate the impact of PAF on intestinal water and protein transport across microvessels.
- To elucidate the role of leukocytes in PAF-mediated microvascular effects.
Main Methods:
- Local intra-arterial infusions of PAF at varying concentrations (4, 20, 40 ng/min) in an animal model.
- Measurement of intestinal transcapillary, lymphatic, and transmucosal water and protein fluxes.
- Assessment of leukocyte adherence to mesenteric venular endothelium and the effect of a specific monoclonal antibody (MoAb IB4).
Main Results:
- PAF administration significantly increased intestinal water and protein fluxes at all tested concentrations.
- PAF elevated venous hematocrit and vascular protein flux, indicating increased capillary leakage.
- PAF promoted leukocyte adherence, and treatment with MoAb IB4 attenuated these PAF-induced microvascular changes.
Conclusions:
- PAF enhances fluid and protein filtration across intestinal capillaries.
- Adherent leukocytes play a partial but significant role in mediating the microvascular effects of PAF in the intestine.