Analysis of the Experimental Lesion of Connective Tissue Produced by a Complex of C Polysaccharide From Group a Streptococci

Abstract

A chronic, remittent, multinodular lesion of the connective tissue of rabbits is induced with a peptide-C polysaccharide complex from the cell walls of beta hemolytic streptococci (1). Some form of hypersensitivity is the most obvious explanation to invoke for the mechanism of this lesion, but histological, immunological, and enzymatic analyses do not support this concept (2-4).If the toxic manifestations of a bacterial component are dependent upon a mechanism of hypersensitivity, susceptibility of animals should increase with age. This is based upon the assumption that the immunological competence of the neonatal animal is not well developed, and that continued exposure to crossreactive bacterial antigens in the environment will increase the hypersensitive state of the animal as it ages. Toxicity of endotoxins from Gram-negative bacteria, for example, increases directly with age, and most of the toxic effect has an allergic basis (5).The influence of age of the animal on the chronic relapsing lesion produced by streptococcal components was studied to obtain further evidence of the role of hypersensitivity in this reaction. The age distribution of susceptibility indicates that the chronic nodular lesion involves some physiological maturation besides the immune response. The experiments were designed to follow the evolution of the allergic and of the relapsing nodular reactions, from neonatal through adult life, in rabbits sensitized by specific active or passive sensitization, or sensitized by natural contact with microbial antigens in their environment, cross-reactive with Group A streptococcal components.

Persistence of Group a Streptococcal Cell Walls Related to Chronic Inflammation of Rabbit Dermal Connective Tissue

“…This indicates that the cell wall material can persist in some animals for an indefinite period of time until an adequate inflammatory response is invoked. Presumably, these animals eventually would have developed lesions, since in other studies with this dose of cell wall material an occasional animal would remain completely negative for as long as 8 wk after injection and then develop a typical primary nodular lesion followed by exacerbations (3,4). The fact that Group A cell wall fragments can reside in tissue within macrophages for a long period before a tissue response is apparent, is one of the most significant observations of this study.…”

Treatment of experimental erosive arthritis in rats by injection of the muralytic enzyme mutanolysin.

“…In addition, injection of filtrates ofS. albus or group C streptococcal phage-associated lysin directly into a cell wall injection site in rabbit skin results in a decrease in the severity and duration of dermal lesions (27).…”

Pathogenesis of Group A Streptococcal Infections

“…Murphy and Swift reported focal heart lesions in rabbits (371-374). Schwab and colleagues studied group A streptococcal cell walls and peptidoglycan-polysaccharide complexes in mice and rats which developed carditis, arthritis, or uveiitis (114,115,166,191,192,213,253,295,473,(474)(475)(476)548). None of the models previously investigated have been used to adequately study the mechanisms of pathogenesis in rheumatic fever.…”

“…One of the complications of developing a model of infection which leads to rheumatic fever symptoms is that animals are not easily infected and once infected do not maintain an infection for a lengthy period of time. Therefore, most animal models which have been reported have relied on immunization of rabbits, mice, rats, and monkeys (114,115,166,191,192,(473)(474)(475)(476)548). A review by Unny and Middlebrook on rheumatic carditis described many early studies of rheumatic fever in animals, noting the streptococcal antigen used, the type of immunization, and the ani- mal tested (525).…”