Abstract:

INTRODUCTION. Although much is known today about the mechanisms by which virulent Staphylococcus aureus induce tissue lesions and cause clinical manifestations in mammals, our knowledge of the role played by “professional” phagocytes in host and parasite interrelationships in staphylococcal infections, is not fully understood. The extensive literature on staphylococci and their role in human disease has been the subject of several excellent comprehensive reviews (Whipple, 1965; Cohen, 1972; Jeljaszewicz, 1976). It is accepted that the interception of staphylococci by granulocytes (PMNs) takes place soon after the penetration of the cocci into the tissues. This involves the release of chemotactic factors, by the bacteria themselves (Pusell et al., 1975) or the activation, by staphylococcal factors, of chemotactic agents from complement (Ginsburg and Quie, 1980). Subsequent phagocytosis is markedly enhanced by opsonins (Koenig, 1972; Ekstadt, 1974), and in most cases the engulfed bacteria may be killed intracellularly by a variety of bactericidal agents generated by activated PMNs (Klebanoff, 1972). It is also suggested that certain lysosomal enzymes, which are released into the phagolysosome, may digest the staphylococcal cells (Cohn, 1963a; De Voe et al., 1973; Ginsburg and Sela 1976; Ginsburg, 1979) (see Sections II.B and VI). Several reports have, however, shown that intracellular staphylococci may sometimes survive within PMNs, where they multiply and eventually kill the cell (Koenig, 1972; Cohen, 1972; Pearce et al., 1976). Surprisingly, very little is known about the fate and mechanism of biodegradation of staphylococcal cell constituents, once they have been sequestered within the phagolysosomes of leucocytes. The importance of this field of research stems from the findings that non-biodegradable cell wall components of a variety of microbial species may persist within macrophges for prolonged periods, to trigger chronic infiammatory sequelae (Dannenberg, 1968; Kanai and Kondo, 1974; Ginsburg et al., 1975a; 1975b; 1976a; Ginsburg and Sela, 1976; Adams, 1976; Page et al., 1978; Ginsburg, 1979). The inability of “professional” phagocytes to degrade intracellular bacteria may be due (1) to the presence, on the surface of certain microorganisms, of shielding capsular material (Dossett et al., 1969; Smith, 1977; Wilkinson, et al., 1979; Densen and Mandell, 1980), (2) to the lack of fusion between lysosomes and phagosomes (Goren et al., 1976; Densen and Mandell, 1980), (3) to the production of leucocidins (Gladstone and Van Heyningen, 1957; Woodin, 1960; Ginsburg, 1970; Van Heyningen, 1970; Bernheimer. 1970; Ginsburg, 1972), (4) to the lack of adequate lysosomal enzymes capable of cleaving bacterial peptidoglycans (Dannenberg, 1968; Ginsburg, 1972; Ginsburg and Sela, 1976; Page et al., 1978; Ginsburg, 1979), or (5) to the presence, in serum and in inflammatory exudates, of agents which interfere with the interaction of bactericidal and bacteriolytic age with engulfed bacteria. These fields were comprehensively reviewed EW’ Jeljaszewicz, 1976; Smith, 1977; Ginsburg, 1979; and by Densen and Mandell, 1980. During the last 8 years our laboratory has been studying the host- and-parasite interrelationships in streptococcal and staphylococcal infections using biochemical, electron microscopical and tissue culture techniques. In particular we studied the mechanisms by which leu- cocytes and their isolated lysosomal agents bring about the degrada- tion of staphylococcal cell wall components, and the role which may be played by such degradation products in the initiation of chronic inflammation. The present report is an updated overview of these studies.