Journal of Applied Physiology, Vol 59, Issue 6 1726-1732, Copyright © 1985 by American Physiological Society
Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X
K. E. Burhop, R. A. Proctor, R. B. Helgerson, C. H. Raetz, J. R. Starling and J. A. Will
The chemical structure of the biologically active lipid A portion of
Gram-negative endotoxin [lipopolysaccharide (LPS)] has recently been
elucidated. This was greatly facilitated by the isolation of an Escherichia
coli mutant that accumulates large quantities of lipid X, a novel
monosaccharide precursor of lipid A (C. R. H. Raetz, Rev. Infect. Dis. 6:
463-471, 1984). We now report on the activity of lipid X in the lung-lymph
model in sheep. We have measured the response to cumulative bolus
injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six
chronically instrumented unanesthetized sheep. Lipid X at a total dose of
40 micrograms/kg produced a biphasic pattern of changes. The early phase
was characterized by a rapid transient pulmonary arterial constrictive
response that was dose dependent, accompanied by a delayed transient
increase in lung-lymph flow (P less than 0.05), a significant (P less than
0.01) decrease in arterial blood O2 tension and an increase (P less than
0.05) in lung-lymph protein clearance. Protein permeability changes in the
first phase are not usually seen following endotoxin injection. However,
like endotoxin, lipid X also produced a late phase (3-6 h later) of
increased lung vascular permeability to fluid and protein as reflected by
significant (P less than 0.05) increases in both lung-lymph flow and
lung-lymph protein clearance in the presence of stable pulmonary vascular
pressures at or below base-line levels. We conclude that some of the
pulmonary pressor activity of the endotoxin molecule can be attributed to
the lipid X substructure. Furthermore, changes in vascular permeability may
also be initiated by this substance.
