LIPID-A AS BIOLOGICALLY-ACTIVE MOIETY IN BACTERIAL-ENDOTOXIN (LPS)-INITIATED GENERATION OF PROCOAGULANT ACTIVITY BY PERIPHERAL-BLOOD LEUKOCYTES

  • 1 January 1977
    • journal article
    • research article
    • Vol. 49  (6) , 947-956
Abstract
Preparations of rabbit or human leukocytes, when incubated with bacterial endotoxins (lipopolysaccharides, LPS) are stimulated to generate a procoagulant tissue factor activity (TFa). As LPS was shown to consist of specific repeating oligosaccharide side chains (O-antigen) linked to a central polysaccharide core region that is, in turn, linked to the lipid region of the molecule (lipid A), the biochemical requirement of the LPS necessary for generation of TFa was examined. Using preparations of LPS from mutant strains of bacteria, which contain varying amounts of polysaccharide in relation to lipid A, it was demonstrated that activity is associated with the lipid A region of the LPS molecule. These observations were confirmed using isolated lipid A, which is a potent stimulator of TFa, and a native protoplasmic polysaccharide that is devoid of lipid A and without detectable TFa stimulatory activity. Modification of LPS by treatment with mild alkali abrogated its capacity to stimulate TFa generation. Such altered preparations of LPS partially inhibit the stimulatory effect of native LPS. Treatment of LPS (or lipid A) with the antibiotic polymyxin B substantially inhibited the stimulatory effect of LPS.