Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice

Liver. 2000 Dec;20(6):465-74. doi: 10.1034/j.1600-0676.2000.020006465.x.


Background/aims: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony-stimulating factor (M-CSF/CSF-1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M-CSF to lipopolysaccharide (LPS)-induced cytokine expression and neutrophil infiltration in the liver.

Methods: We investigated the effects of LPS administration in M-CSF-deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT-PCR. Neutrophil infiltration in the liver was also examined.

Results: After LPS administration, cytokine production and expression of LPS receptors, such as CD14 and scavenger receptor class A (MSR-A), were induced at lower levels in op/op mice than those in littermate mice. Neutrophil infiltration in the liver of op/op mice did not differ significantly from that of littermate mice. Anti-IL-8 receptor homologue and anti-C5a receptor antibody reduced the number of infiltrating neutrophils.

Conclusions: These findings indicate that deficient macrophage activation following LPS injection in op/op mice is associated with decreased expression of CD14 and MSR-A in the liver. Thus, M-CSF plays a critical role in LPS-induced macrophage activation but does not exert a dominant role in neutrophil infiltration in the liver.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Bacterial Proteins / biosynthesis*
  • Chemokine CXCL2
  • Chemokines / immunology
  • DNA Primers / chemistry
  • Fluorescent Antibody Technique, Indirect
  • Interleukin-1 / biosynthesis*
  • Interleukin-8 / immunology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Kupffer Cells / pathology
  • Lipopolysaccharide Receptors / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Liver / drug effects
  • Liver / pathology
  • Lymphocyte Activation
  • Macrophage Colony-Stimulating Factor / deficiency
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / physiology*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology*
  • Osteopetrosis / genetics
  • Osteopetrosis / immunology
  • Osteopetrosis / metabolism*
  • RNA / analysis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Antibodies, Blocking
  • Bacterial Proteins
  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • DNA Primers
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Transport Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • msrA protein, Staphylococcus epidermidis
  • RNA
  • Macrophage Colony-Stimulating Factor