Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X.

Area of Science:

• Biochemistry
• Immunology
• Physiology

Background:

• The biologically active lipid A component of Gram-negative endotoxin (lipopolysaccharide, LPS) has a defined chemical structure.
• Lipid X, a monosaccharide precursor of lipid A, was isolated from an Escherichia coli mutant.
• Lipid X's role in endotoxin's biological activity requires further investigation.

Purpose of the Study:

• To investigate the physiological activity of lipid X in a sheep lung-lymph model.
• To determine if lipid X contributes to the pulmonary effects of endotoxin.

Main Methods:

• Six chronically instrumented, unanesthetized sheep were used.
• Cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) were administered.
• Pulmonary arterial pressure, lung-lymph flow, arterial blood O2 tension, and lung-lymph protein clearance were measured.

Main Results:

• Lipid X induced a biphasic response.
• An early phase showed dose-dependent pulmonary arterial constriction, decreased O2 tension, and increased lung-lymph protein clearance.
• A late phase (3-6 hours) demonstrated increased lung vascular permeability to fluid and protein, similar to endotoxin effects.

Conclusions:

• The lipid X substructure contributes to the pulmonary pressor activity of endotoxin.
• Lipid X can initiate changes in vascular permeability, independent of endotoxin.