Relationship between increased vascular permeability and extravascular albumin clearance in rabbit inflammatory responses induced with Escherichia coli.

Intradermal injections of killed Escherichia coli are known to cause a variety of pathophysiological changes in the microcirculation that facilitate the extravasation of plasma constituents into the interstitium. In an attempt to learn more of the factors that regulate the magnitude and duration of inflammatory edema, we have focused on the relationship between the extravasation of protein into the interstitium and the removal of extravascular protein from the lesion sites. Vascular permeability changes have been assessed by the local accumulation of systemically administered [131I] or [125I]-albumin and extravascular protein clearance measured by monitoring the disappearance of [125I]-albumin from the same sites. Radioactivity was quantitated with an external gamma-scintillation probe or by punching out the lesion sites in sacrificed animals and counting in a gamma-spectrometer. Scintillation probe measurements of the net accumulation of intravenously administered [125I]-albumin in E. coli-induced skin lesions revealed that the extravasation of albumin was greater than the clearance of protein from the same sites. Comparisons of the removal rates of albumin injected directly into the E. coli sites revealed that, despite increases in vascular permeability amounting to 170 to 700% of control values, the mobilization of deposited albumin was no greater than that from control tissues that received saline; in fact with high concentrations of E. coli (10(8) injected/site) the mobilization of protein from the lesions was significantly reduced. The systemic administration of 055:B5 endotoxin (0.3, 1.6, or 3.3 micrograms/kg) also suppressed the clearance of albumin from skin. In contrast to these results, 300 to 1500% increases in vascular permeability induced with other inflammatory stimuli including thermal injury, high concentrations of bovine serum albumin, or bradykinin, resulted in enhanced clearance of extravascular protein from lesion or injection sites. These experiments suggest that an inability to effectively mobilize extravascular protein from the inflammatory focus could be a major contributing factor in regulating edema in inflammatory reactions induced with E. coli and may possibly contribute to the edema associated with septicemia.