Defective prostaglandin synthesis by C3H/HeJ mouse macrophages stimulated with endotoxin preparations.

Macrophages obtained from C3H/HeN mice produced significant amounts of prostaglandin E when exposed to phenol-extracted lipopolysaccharides (LPS), whereas macrophages from C3H/HeJ mice were unresponsive. The lipid A fraction from phenol-extracted LPS was an effective inducer or prostaglandin synthesis by macrophages from C3H/HeN mice. The polysaccharide portion of the LPS molecule had no effect. In contrast, the C3H/HeJ macrophages did not produce prostaglandin E in response to the lipid A moiety of phenol-extracted LPS. LPS prepared by butanol extraction stimulated the production of prostaglandin E by macrophages from both C3H/HeN and C3H/HeJ mice. The component of butanol-extracted LPS that stimulated the C3H/HeJ macrophages was shown to be a lipid A-associated protein. Further studies demonstrated a correlation between prostaglandin production by the macrophages of these two strains of mice in response to butanol- and phenol-extracted LPS and the lethal effects of the endotoxin preparations.