Strain Differences in Local Hemorrhagic Response (Shwartzman-Like Reaction) of Mice to a Single Intradermal Injection of Bacterial Polysaccharides

Abstract

A survey of inbred strains of mice was made to determine whether the phenomenon of dermal hemorrhagic necrosis, as described in rabbits by Shwartzman, could be elicited in mice by bacterial polysaccharide preparations of demonstrated activity in rabbits. The polysaccharide preparations used were obtained from cultures of S. marcescens, S. typhosa, Ps. aeruginosa, and H. pertussis. Ten of the strains tested were unreactive. Three strains of mice and one F1 hybrid subline developed a hemorrhagic lesion at the site of injection of a single, relatively high intradermal dose of polysaccharide. Some increase in incidence of hemorrhagic lesions was obtained when the intradermal dose was followed in 24 hours by an intravenous injection. In the gross and microscopically, the skin lesion produced in mice resembled the Shwartzman reaction in rabbits. An adrenergic blocking agent, SY-28, and an anticoagulant drug, coumadin, both of which block the dermal Shwartzman reaction in rabbits, also blocked the hemorrhagic skin reaction in mice.

The Susceptibility of Mice to Bacterial Endotoxins

“…The fact that various colonies of mice differ so consistently in their susceptibility to endotoxins appears at first sight to support the commonly held view that this characteristic is genetically determined (6)(7)(8). Some of our findings, however, point to the role of the bacterial flora in conditioning the response of animals to endotoxins.…”

The Extension of the Shwartzman Phenomenon to the Mouse and Some Ecological Determinants of the Single-Injection Reaction

“…(d) Inhibition of the Reaction with Anticoagulant Therapy.--Kelly et al (7) have reported that the skin reaction observed by them was blocked by pretreatment of the mice with the anticoagulant drug eoumadin. We have obtained similar results with two anticoagulants, dicumarol and heparin.…”

“…The * This paper is a condensed report drawn from a dissertation, "The Extension of the frequency of these hemorrhages was inconstant, but high enough to enforce our attention and prompt the hope that they might be better understood. Although the hemorrhages were not being produced by the usual two injections characteristic of the Shwartzman reaction, and thus presented a puzzle, they were produced in a mouse stock related to one of the partially competent strains described by Kelly et al (7). The Shwartzman phenomenon was thus considered as bearing some relationship to these observations.…”

“…In another system, Stone and Freund (6) used the lip as the reactive site and showed that presensitization of the mice with foreign proteins enhanced the reactions. Kelly and her group (7), finding that three out of fourteen inbred mouse strains were partially reactive to the classical series of endotoxin injections suggested that genotype was an important parameter. In contrast, however, Oliveira-Lima (8) demonstrated the reaction in Webster Swiss mice, a known random-bred and allegedly refractory strain, but only when mice older than 8 months were used.…”

Possible Significance of Bradykinin in the Shwartzman and Other Phenomena*

“…The possibility that trasylol may not prove effective in inhibiting the reaction a t the phase employed is to be expected since this agent is not a direct bradykinin antagonist but an inhibitor of kallikreinsZ6. 2 6 and, therefore, ineffective in neutralizing the activities of bradykinin which is already present in its active form. The time relationship between the injection of potentiating or inhibitory substances and the provocative LPS injection indicates that these substances can influence the reaction only when introduced at critical phases of its course.…”