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Lipid A as the biologically active moiety in bacterial endotoxin (LPS)-
initiated generation of procoagulant activity by peripheral blood
leukocytes
J Niemetz and DC Morrison
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 has been 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), we have examined the biochemical
requirement of the LPS necessary for generation of TFa. Using preparations
of LPS from mutant strains of bacteria, which contain varying amounts of
polysaccharide in relation to lipid A, we have demonstrated that activity
is associated with the lipid A region of the LPS molecule. These
observations have been confirmed using isolated lipid A, which is a potent
stimulator of TFa, as well as a native protoplasmic polysaccharide that is
both 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. In addition, such altered preparations of LPS
partially inhibit the stimulatory effect of native LPS. Similarly,
treatment of LPS (or lipid A) with the antibiotic polymyxin B substantially
inhibited the stimulatory effect of LPS.
Volume 49,
Issue 6,
pp. 947-956,
06/01/1977
Copyright © 1977 by The American Society of Hematology
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