Interactions of the complement system with endotoxic lipopolysaccharide: the generation of an anaphylatoxin

Abstract

The incubation of endotoxin derived from Veillonella alcalescens or Serratia marcescens with fresh guinea-pig serum leads to the production of a factor which contracts guinea-pig ileum. This factor has been identified as an anaphylatoxin since it causes tachyphylaxis and its activity is abolished by antihistamines. The activity is not generated if the serum has been heat inactivated or if the reaction is carried out at 0° or in the presence of EDTA. The complement system (C′) is implicated in the generation of this anaphylatoxin by the above data and by static and kinetic C′ consumption studies which show a correlation between the disappearance of the late acting C′ and the appearance of gut contracting activity. Endotoxoid preparations which do not utilize C′ are not able to generate anaphylatoxin. A further parallel between classical anaphylatoxin and the endotoxin-generated factor is found in the pattern of mammalian sera which support the reaction. In view of the similarities between the biological properties of anaphylatoxin and the syndrome of endotoxic shock, it is suggested that some of the manifestations of the latter might result from an interaction between endotoxin and the C′ system leading to the generation of an anaphylatoxin.