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PMID:12055258

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Citation

Fierer, J, Swancutt, MA, Heumann, D and Golenbock, D (2002) The role of lipopolysaccharide binding protein in resistance to Salmonella infections in mice. J. Immunol. 168:6396-403

Abstract

Polymorphonuclear leukocytes (PMN) and LPS-binding protein (LBP) are both components of the innate immune system. LBP is a plasma protein that binds to lipid A and enhances the biological activity of LPS 100- to 1000-fold. Recently it was reported that LBP-deficient mice are more susceptible to Salmonella typhimurium infection. Here we report that LBP KO mice are more susceptible to Salmonella peritonitis, but not to oral or i.v. infection. LBP knockout (KO) mice responded normally to i.p. injections of Staphylococcus aureus and casein, but not to i.p. injection of S. typhimurium or Salmonella LPS. Mice with a mutation in Toll-like receptor 4 (C3H/HeJ) have a similar defect in PMN chemotaxis. In normal mice S. typhimurium stimulated production of the CXC chemokines macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant, but levels of cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2 were greatly reduced in the LBP KO mice. LBP KO mice pretreated with casein to attract PMN in an LBP-independent manner were more resistant to Salmonella infection, but neutropenic mice were not protected by casein. Splenic TNF-alpha mRNA levels were also lower in LBP KO than in control mice infected with Salmonella. Since TNF-alpha can activate PMN, LBP KO mice may have both fewer and less active PMN in the first few hours after Salmonella are injected, making LBP KO mice more susceptible. This work confirms the importance of PMN in resistance to Salmonella infections and shows that this is facilitated by LBP.

Links

PubMed

Keywords

Acute-Phase Proteins; Administration, Oral; Animals; Antigens, Bacterial/administration & dosage; Antigens, Bacterial/immunology; Ascitic Fluid/immunology; Ascitic Fluid/pathology; Carrier Proteins/biosynthesis; Carrier Proteins/blood; Carrier Proteins/genetics; Carrier Proteins/physiology; Enteritis/genetics; Enteritis/immunology; Genetic Predisposition to Disease; Immunity, Innate/genetics; Injections, Intraperitoneal; Injections, Intravenous; Lipopolysaccharides/metabolism; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Neutropenia/genetics; Neutropenia/immunology; Peritonitis/genetics; Peritonitis/immunology; Peritonitis/pathology; Salmonella Infections, Animal/genetics; Salmonella Infections, Animal/immunology; Salmonella Infections, Animal/mortality; Salmonella typhimurium/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CXCL2

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:35683)

Seeded From UniProt

complete

MOUSE:GROA

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:35683)

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0002232: leukocyte chemotaxis involved in inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

  • occurs_in:(EMAPA:16138)

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

  • regulates_o_occurs_in:(EMAPA:18767)

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0032722: positive regulation of chemokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0032496: response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

  • occurs_in:(EMAPA:16138)

Seeded From UniProt

complete

MOUSE:LBP

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:35770)|part_of:(EMAPA:35683)

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0050829: defense response to Gram-negative bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

Seeded From UniProt

complete

MOUSE:LBP

acts_upstream_of_or_within

GO:0090023: positive regulation of neutrophil chemotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857975

P

  • regulates_o_occurs_in:(EMAPA:16138)

Seeded From UniProt

complete

MOUSE:TLR4

acts_upstream_of_or_within

GO:0032496: response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857718

P

  • occurs_in:(EMAPA:16138)

Seeded From UniProt

complete

MOUSE:CXCL2

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:35683)

Seeded From UniProt

complete

MOUSE:TLR4

acts_upstream_of_or_within

GO:0032496: response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857718

P

occurs_in:(EMAPA:16138)

Seeded From UniProt

complete


See also

References

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