Permeability factor-like skin reaction in rabbits induced by endotoxin of Salmonella sp.

An inflammatory skin reaction similar to the permeability factor (PF) described for the thermolabile (TL) enterotoxin of Escherichia coli was induced in rabbits inoculated intradermally with supernatants from cultures of Salmonella typhimurium and S. enteritidis. This PF-like activity was observed with both crude supernatants as well as those which were submitted to gel filtration through Sephadex G-100. PF-like activity was found only in fraction 1 (F1) of the chromatographed materials. It was resistant to boiling, proteolytic enzymes and wide variations of pH. Serological studies based on agglutination and immunodiffusion tests demonstrated that F1 materials were closely related to the somatic antigen of group B Salmonella. No specific TL activity, as detected by the Y-1 adrenal cell assay and the passive immune haemolysis test, could be demonstrated. Furthermore, F1 materials were not enterotoxigenic as assayed by the rabbit ileal loop assay, and no neutralization of PF-like activity could be obtained in tests carried out using F1 preparations pre-incubated with either anti-F1 or cholera antitoxin. Based upon these findings, it seems reasonable to suppose that most PF reactions, already reported as being caused by a TL-like enterotoxin produced by Salmonella, are probably due to endotoxin. In fact, this possibility was reinforced by the Sanarelli-Shwartzman phenomenon which was produced in rabbits inoculated with F1 materials.

A study of the large heparin requirements in the generalized Shwartzman reaction.

The heparin requirements necessary to inhibit intravascular fibrin deposition and soluble fibrin monomer (FM) formation in the generalized Shwartzman reaction (GSR) were evaluated. Fibrin deposition was measured by a quantitative technique utilizing 125I-labeled rabbit fibrinogen. FM was measured semiquantitatively by gel exclusion chromatography and by the serial dilution protamine sulfate (SDPS) test. There was a fourfold increase in heparin requirement 5 min after compared with 5 min before the second dose of endotoxin. This increase in heparin requirement was not related to thrombin elaboration, since FM was not found until more than 1 hr after the second dose of endotoxin. Neither was there any evidence of diminished sensitivity to the anticoagulant effect of heparin. The heparin requirements in the GSR rabbits were found to be in excess of those needed to neutralize a defibrinating dose of thrombin. It was concluded that a potent, heparin-resistant clotting activity developed within 5 min of the second endotoxin injection. The mechanism by which the activity caused the gradual elaboration of a thrombin-like enzyme is diffucult to explain on the basis of traditional coagulation reactions. The apparent role of white cells is discussed.