Mouse Soluble CD14 Truncated at Amino Acid 71 in Transgenic Mice: Preventive Effect on Endotoxin-Mediated Toxic Shock

Abstract

Mouse soluble CD14 truncated at amino acid 71 (N71) contains the lipopolysaccharide (LPS)-binding sequence. Transgenic mice carrying α1-antitrypsin (AT) promoter-N71 fusion genes, designated AT363-1 and AT363-2, were produced. These mice constitutively produced elevated levels of N71. The concentration of LPS in sera after intraperitoneal LPS injection was lower in AT363-1 mice than in nontransgenic mice. The expression of N71 mRNA was enhanced by subcutaneous turpentine oil injection. The levels of serum LPS and tumor necrosis factor-alpha (TNF-α) after intraperitoneal LPS injections were lower in AT363-1 mice than in nontransgenic mice. Cell surface TNF-α and CD14 expression in exudate peritoneal macrophages prepared by intraperitoneal injection of proteose peptone and then LPS were higher in AT363-1 mice than in nontransgenic mice. Neutrophil infiltration in the liver after induction of the generalized Shwartzman reaction was lower in AT363-1 mice than in nontransgenic mice. Lethality of the Shwartzman reaction was significantly lower in AT363-1 than in nontransgenic mice. These findings suggest that the endotoxin-binding protein (N71) from CD14 prevents endotoxin-mediated toxic shock.