Human acyloxyacyl hydrolase is an unusual lipase, found in phagocytic cells, that removes acyl chains from bacterial lipopolysaccharides (LPS) and glycerolipids. It is a heterodimer in which two glycosylated peptides are linked by disulfide bonding. The large subunit contains the active site serine, while the smaller subunit has striking sequence similarity to the saposins, peptide cofactors for several sphingolipid hydrolases. Since rabbits and mice are widely used for studies of LPS—animal interactions, we asked if murine and lapine AOAHs resemble the human enzyme. We report here that murine and lapine AOAHs share the distinctive features of the human AOAH primary sequence and have similar affinity for LPS. The structure of this unusual lipase appears to have been highly conserved.
References
1.
Kotani S., Takada H.Structural requirements of lipid A for endotoxicity and other biological activities — An overview. Adv Exp Med Biol1990; 256: 13—44.
2.
Hall CL, Munford RSEnzymatic deacylation of the lipid A moiety of Salmonella typhimurium lipopolysaccharides by human neutrophils. Proc Natl Acad Sci USA1983; 80: 6671—6675.
3.
Erwin AL, Munford RSDeacylation of structurally diverse lipopolysaccharides by human acyloxyacyl hydrolase. J Biol Chem1990; 265: 16444—16449.
4.
Munford RS, Hunter JPAcyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides, has phospholipase, lysophospholipase, diacylglycerollipase, and acyltransferase activities in vitro. J Biol Chem1992; 267: 10116—10121.
5.
Munford RS, Hall CLDetoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science1986; 234: 203—205.
6.
Pohlman TH, Munford RS, Harlan JMDeacylated lipopolysaccharide inhibits neutrophil adherence to endothelium induced by lipopolysaccharide in vitro. J Exp Med1987; 165: 1393—1402.
7.
Hagen FS, Grant FJ, Kuijper JL, Slaughter CA, Moomaw CR, Orth K. et al. Expression and characterization of recombinant human acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides . Biochemistry1991; 30: 8415—8423.
8.
Staab JF, Ginkel DL, Rosenberg GB, Munford RSA saposin-like domain influences the intracellular localization, stability, and catalytic activity of human acyloxyacyl hydrolase. J Biol Chem1994; 269: 23736—23742.
9.
Munford RS, Sheppard PO, O'Hara PJSaposin-like proteins (SAPLIP) carry out diverse functions on a common backbone structure. J Lipid Res1995; 36, 1653—1663.
10.
Munford RS, Hall CLUptake and deacylation of bacterial lipopolysaccharides by macrophages from normal and endotoxinhyporesponsive mice. Infect Immun1985; 48: 464—473.
11.
Erwin AL, Munford RSPlasma lipopolysaccharide-deacylating activity (acyloxyacyl hydrolase) increases following lipopolysaccharide administration to rabbits. Lab.Invest1991; 65: 138—144.
12.
McDermott CM , Cullor JS, Fenwick BWIntracellular and extracellular enzymatic deacylation of bacterial endotoxin during localized inflammation induced by Escherichia coli. Infect Immun1991; 59: 478—485.
13.
Coulthard MG , Swindle J., Munford RS, Gerard RD, Meidell RSAdenovirus-mediated transfer of a gene encoding acyloxyacyl hydrolase (AOAH) into mice increases tissue and plasma AOAH activity . Infect Immun1996; 64: 1510—1515.
14.
Cody MJ, Salkowski CA, Henricson BE, Detore GR, Munford RS, Vogel SNEffect of inflammatory and anti-inflammatory stimuli on acyloxyacyl hydrolase gene expression and enzymatic activity in murine macrophages. J Endotoxin Res1997; 4: 371—379.
15.
Li J., Aderem A.MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates . Cell1992; 70: 791—801.
16.
Slonina AE, Scott TC, Lehrman MAGene inactivation in Lec35.1 (mannosylation-defective) Chinese hamster ovary cells. J Biol Chem1993; 268: 6729—6733.
17.
Andersson S. , Davis DN, Dahlback H., Jornvall H., Russell DWCloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem1989; 264: 8222—8229.
