The physical-chemical characterization and biologic activity of serum released lipopolysaccharides.
As a result of the incubation of Escherichia coli in normal human serum, a finite fraction of LPS is released from the bacterial membrane. Approximately half of the LPS released by the action of serum (S-LPS) exists in association with serum proteins in a lower m.w. form than that manifest in phenol-water extracted LPS preparations. The two major LPS-serum protein complexes have apparent Mr of 68 and 32 kDa. The LPS subunit heterogeneity of S-LPS, however, does not appear to differ significantly from LPS retained on the bacteria after serum treatment, or from LPS derived by lysis of whole cells. The biologic activities of S-LPS and phenol-water extracted LPS examined in these studies, differed significantly. In contrast to phenol-water extracted LPS, S-LPS was 1) reduced in lethal toxicity for sensitized mice; 2) reduced in Limulus reactivity; 3) a more potent murine splenocyte mitogen; 4) reduced in the capacity to elicit extracellular, but not membrane-associated IL-1; and 5) reduced in the ability to mediate TNF production. These data suggest that humoral "detoxification" of LPS may involve, in part, the formation of LPS-serum protein complexes with reduced capacities to elicit extracellular cytokine production, whereas the immunomodulatory effects of LPS appear to be enhanced.
Tesh
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Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Morrison
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D000276:Adjuvants, Immunologic / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001798:Blood Proteins / Q000302:isolation & purification* / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000097:blood* / Q000302:isolation & purification / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D001798:Blood Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha