6533b7d8fe1ef96bd126a177

RESEARCH PRODUCT

The Role of the Classical Pathway for the Bactericidal Effect of Normal Sera Against Gram-Negative Bacteria

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Many gram-negative bacteria are killed after treatment with normal serum. This phenomenon was already described in 1889 by Buchner. The serum-bactericidal effect is abolished when serum has been incubated for 30 min at 56° C. Gram-positive bacteria are less sensitive than gram-negative bacteria to direct killing, although gram-positive cocci are opsonized by the action of serum mediated by antibodies and complement (Inoue et al. 1968; Johnston et al. 1969). Normal sera exhibit bactericidal and bacteriolytic properties against some gramnegative strains; whereas, other gram-negative strains are serum resistant. It has been shown that serum from C4-deficient guinea pigs is able to kill some gram-negative rods, due to the activation of the alternative pathway (Bjornson and Bjornson 1977; Root et al. 1972). Other rods are resistant or killed slowly when the classical complement pathway was abolished by removing Ca++ with EGTA (Traub and Kleber 1976). Furthermore, it was found that most of the smooth strains of gram-negative bacteria are serum resistant; whereas, the corresponding rough forms are extremely serum sensitive (Muschel and Larsen 1970; Rowley 1968; Good and Day 1977). These investigations provided evidence that the composition of the bacterial surface may influence the reaction of the bacteria with the lytic system (Sterzl et al. 1964). The bacteriolytic properties of serum are mediated by the deposition or insertion of the assembled terminal proteins of the complement cascade, C5b-9 (the so-called membrane attack complex, MAC), into the bacterial envelope. The antibody-dependent activation of the classical complement pathway as well as activation of the alternative pathway by bacteria has been extensively studied. However, several strains are rapidly killed in nonimmune sera. Furthermore, it was reported that Cl is absorbed to Mycoplasma pneumoniae in the absence of antibodies; the direct interaction with Cl and the activation of the classical C cascade had even more biological consequences for these bacteria than did activation of the alternative pathway (Bredt et al. 1977). The experiments presented in this study indicate that the antibody-independent interaction of Cl with bacteria and bacterial membrane constituents is a common phenomenon leading to the activation of the complement system and subsequently to the killing of these bacteria.