Mouse soluble CD14 truncated at amino acid 71 in transgenic mice: preventive effect on endotoxin-mediated toxic shock.
Mouse soluble CD14 truncated at amino acid 71 (N71) contains the lipopolysaccharide (LPS)-binding sequence. Transgenic mice carrying alpha1-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-alpha) after intraperitoneal LPS injections were lower in AT363-1 mice than in nontransgenic mice. Cell surface TNF-alpha 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.
Higuchi
Y
Y
Department of Pathology, Oita Medical University, Oita, Japan. higuchi@oita-med.ac.jp
Hijiya
N
N
Matsuura
K
K
Yasui
A
A
Uchida
T
T
Yamamoto
S
S
D000818:Animals; D000906:Antibodies / Q000097:blood; D001202:Ascitic Fluid / Q000737:chemistry; D015152:Blotting, Northern; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D007509:Irritants / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012772:Shock, Septic / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D012790:Shwartzman Phenomenon / Q000235:genetics / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D014425:Turpentine / Q000494:pharmacology; D015854:Up-Regulation
D000906:Antibodies; D007509:Irritants; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D014425:Turpentine