title: Inhibition of macrophage priming by sulfatide from Mycobacterium tuberculosis.
abstract: Sulfatide from the outer surface of Mycobacterium tuberculosis blocked priming in cultured human monocytes. Monocytes were primed in vitro with either lipopolysaccharide (LPS) or interferon-gamma. Primed monocytes released increased amounts of superoxide anion (O2-) when stimulated with formyl-methionyl-leucyl-phenylalanine or with phorbol myristate acetate. Primed monocytes also showed increased phagocytosis of sheep erythrocytes and increased release of interleukin 1. When primed monocytes were treated with 10 micrograms/ml of sulfatide, these enhanced functions, characteristic of primed monocytes, returned to levels found in unprimed monocytes. (With respect to these functions and others, monocytes or macrophages primed in vitro by exposure to LPS or interferon-gamma resemble macrophages activated in vivo by infection. In vivo, activated macrophages provide non-specific resistance to infection). Inhibition of priming by sulfatide could be detected within 10 min, but maximum effect of sulfatide required 3 to 5 hr. Sulfatide had no effect on O2- release, if it was added after the cells had been stimulated by PMA, suggesting that sulfatide did not inhibit enzymes involved in formation of O2-, but rather that sulfatide inhibited priming. Increasing the amounts of LPS or interferon-gamma did not counteract the effects of sulfatide. Sulfatide did cause monocytes to release some prostaglandin E2 (less than 1 nM), but the amount was not sufficient to inhibit monocyte functions. The effect of sulfatide was not blocked by indomethacin. Other sulfated compounds and other products of mycobacteria did not produce the sulfatide effect. We conclude that M. tuberculosis has on its outer surface a chemical that directly interferes with monocyte priming. In vivo, M. tuberculosis might use sulfatide to block macrophage activation and thereby resist being killed by macrophages.
authors.affiliation: Dental Research Center, College of Dentistry, University of Tennessee, Memphis 38163.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pabst
authors.forename: J M
authors.initials: JM
authors.lastname: Gross
authors.forename: J P
authors.initials: JP
authors.lastname: Brozna
authors.forename: M B
authors.initials: MB
authors.lastname: Goren
mesh_terms: D015232:Dinoprostone; D004306:Dose-Response Relationship, Immunologic; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008563:Membrane Lipids / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors; D037521:Virulence Factors
chemical_list: D006017:Glycolipids; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D011458:Prostaglandins E; D037521:Virulence Factors; D013481:Superoxides; C009355:sulfolipid I; D007371:Interferon-gamma; D015232:Dinoprostone