Macrophage activation by monosaccharide precursors of Escherichia coli lipid A.

Abstract:

:Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate two novel glycolipids, designated X and Y. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3, and lipid Y has the same structure as X, except for the additional presence of a palmitoyl moiety on the N-linked beta-hydroxymyristate. We have examined the activities of X, Y, and several related compounds as activators of macrophages. Both X and Y induce morphological changes (spreading), prostaglandin E2 synthesis, and killing of tumor cells by mouse peritoneal macrophages in vitro, properties with which lipopolysaccharide and lipid A are also endowed. Both glycolipids have similar effects on the macrophage-like mouse cell line J774.1. Selective removal from lipid X of either the ester-linked beta-hydroxymyristate at position 3 or the phosphate at position 1 abolishes activity. Our results show that the monosaccharides X and Y retain some of the properties of intact lipopolysaccharide and lipid A with respect to macrophage activation. Because the structures of X and Y are defined, our findings should facilitate the elucidation of the molecular mechanism of macrophage activation by lipid A.

authors

Nishijima M,Amano F,Akamatsu Y,Akagawa K,Tokunaga T,Raetz CR

doi

10.1073/pnas.82.2.282

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

282-6

issue

2

eissn

0027-8424

issn

1091-6490

journal_volume

82

pub_type

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