HOW ARE CELL-WALL COMPONENTS OF PATHOGENIC MICROORGANISMS DEGRADEDIN INFECTIOUS AND INFLAMMATORY SITES? FACTS AND MYTHS

Abstract:

Introduction. Although a voluminous literature exists today which describes, in great detail, the role played by "professional" phagocytes and by serum components in the killing of pathogenic bacteria in vitro and in vivo (l-7) very surprisingly, however, little is actually known about the fate and mode of disposal of microorganisms once they had been rendered non-viable by the defence systems of the host. It is expected that the rich arsenal of lysosomal hydro- lases, including the key muralytic enzyme lysozyme (LYZ), present in leukocytes and in body fluids might be adequate to biodegrade the complex structures of the microbial cells. Paradoxically, however, the majority of bacteria are highly refractory to LYZ action. There is also some confusion in the literature concerning the distinction between bactericidal and bacteriolytic processes. It is conceivable that while a major degradation of microbial cell walls may be followed by a bactericidal reaction, the mere killing of bacteria either by oxygen radicals (2) or by complement-dependent cytlytic antibodies (7) may not necessarily be accompanied by a significant cell wall degradation. Many experimental models, with laboratory animals, have distinctly shown the persistence, for very long periods, of non-viable bacteria and of undergraded microbial cell wall components, within macrophages, in chronic inflammatory sites (8-l8). Thus, one should categorically differentiate between bactericidal and bacteriolytic phenomena. It is apparent, therefore, that mammalian tissues fail, for still not/fully known reasons, to biodegrade and eliminate microbial cell wall components. Peptidoglycan (PPG)-polysaccharide (PS) complexes derived from microbial cell walls possess distinct pathobiological and and pathophysiological properties (19-21). These include the capacity to activate the complement cascade and to generate chemotactic agents, to induce fever, to activate the respiratory burst in leukocytes and to modulate the immune responses (19-24), to mention only a few of the plethora of functions ascribed to PPG. These properties may also explain the very complex interrelationships which exist between the parasite and the host during microbial infections and the possible reasons for the development of certain post-infectious sequelae, which involve the prolonged persistence of bacterial cell wall components in tissues (10-15).