Effects of local mast cell degranulation on vascular permeability to macromolecules

The suffused noneverted cheek pouch of pentobarbital anesthetized hamsters was used to study the effects of localized, selective mast cell degranulation on vascular permeability. Fluorescein isothiocynate dextran (FITC-D, 70,000 Da) was utilized as a tracer, and intra-vital light microscopy was employed to monitor the formation of vascular leakage sites while direct measurement of plasma and suffusate tracer concentrations were used to monitor tracer clearance. Varying the time at which the FITC-D tracer was injected i.v. relative to the start of the Compound 48/80 suffusion permitted direct determination of the duration of any observed increase in vascular permeability. Selective, local mast cell degranulation was triggered by suffusing the cheek pouch with Compound 48/80 for 10 minutes which stimulated the formation of focal FITC-D leakage sites in the postcapillary venules resulting in increases in [FITC-D]S, [FITC-D]S/[FITC-D]P. 10(-6), and FITC-D clearance. In contrast, suffusion of the cheek pouches with saline failed to trigger the formation of venular FITC-D leakage sites or to promote increases in [FITC-D]S, [FITC-D]S/[FITC-D]P. 10(-6), and FITC-D clearance. The increase in permeability produced by Compound 48/80 was marked but transient (duration less than 20 minutes), and subject to inhibition by treatment with either the H1 receptor antagonist diphenhydramine or the endothelial cell stabilizer isoproterenol. There was no evidence for for a non-histamine mediated or delayed-onset increase in vascular permeability to macromolecules during the course of these experiments.