Antagonistic effects of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein on lipopolysaccharide- induced cytokine release by mononuclear phagocytes. Competition for binding to lipopolysaccharide

Serum proteins play an important role in LPS-induced cell activation. The LPS binding protein (LBP) enhances cellular responses to LPS, whereas the polymorphonuclear leukocyte product bactericidal/permeability-increasing protein (BPI) inhibits LPS-induced cell activation. In this study the influence...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 151; no. 8; pp. 4258 - 4265
Main Authors:	Dentener, MA, Von Asmuth, EJ, Francot, GJ, Marra, MN, Buurman, WA
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Am Assoc Immnol 15-10-1993 American Association of Immunologists
Subjects:	Acute-Phase Proteins Analysis of the immune response. Humoral and cellular immunity Antimicrobial Cationic Peptides Binding, Competitive Biological and medical sciences Blood Proteins - metabolism Blood Proteins - pharmacology Carrier Proteins - metabolism Carrier Proteins - pharmacology Cell Line Cytokines - secretion Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunobiology Limulus Test Lipopolysaccharides - antagonists & inhibitors Lipopolysaccharides - metabolism Membrane Glycoproteins Membrane Proteins Miscellaneous Phagocytes - drug effects Phagocytes - metabolism Regulatory factors and their cellular receptors Human Monocyte Cytokine Bactericidal effect Interleukin 6 Proteins Binding protein Regulation(control) Fixation Lipopolysaccharide Inhibitor Tumor necrosis factor α Interleukin 8 Release Macrophage
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Summary:	Serum proteins play an important role in LPS-induced cell activation. The LPS binding protein (LBP) enhances cellular responses to LPS, whereas the polymorphonuclear leukocyte product bactericidal/permeability-increasing protein (BPI) inhibits LPS-induced cell activation. In this study the influences of LBP and BPI, two proteins with opposite effects, but with considerable sequence homology, on LPS-induced mononuclear phagocytic cell cytokine release was studied. LBP was shown to enhance LPS-induced TNF-alpha, IL-6, and IL-8 release by mononuclear phagocytic cells, whereas BPI inhibited the release of these cytokines. Furthermore, the effects of LBP and BPI on LPS-induced cytokine release by mononuclear phagocytic cells were shown to be counteractive. BPI interfered with the enhancing effect of LBP on the LPS-induced cytokine release. At high LBP to BPI ratios, BPI could no longer inhibit LBP-induced enhancement. In accordance, increasing concentrations of BPI abrogated the LBP effect. Next, it was shown that LBP and BPI compete for binding to LPS by using an assay system that detects binding of free BPI to an anti-BPI mAb. LPS prevented binding of BPI to anti-BPI mAb, whereas preincubation of LPS with LBP prevented the LPS-induced inhibition. Also, it was observed that both BPI and LBP inhibited LPS activity in the chromogenic LAL assay. We conclude from this study that LBP and BPI have counteractive effects on LPS-induced mononuclear phagocytic cell cytokine release by competing for binding to LPS.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.151.8.4258