Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Blocking / pharmacology
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Bacterial Proteins / biosynthesis*
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Chemokine CXCL2
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Chemokines / immunology
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DNA Primers / chemistry
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Fluorescent Antibody Technique, Indirect
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Interleukin-1 / biosynthesis*
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Interleukin-8 / immunology
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Kupffer Cells / drug effects
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Kupffer Cells / metabolism
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Kupffer Cells / pathology
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Lipopolysaccharide Receptors / biosynthesis*
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Lipopolysaccharides / pharmacology
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Liver / drug effects
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Liver / pathology
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Lymphocyte Activation
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Macrophage Colony-Stimulating Factor / deficiency
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Macrophage Colony-Stimulating Factor / genetics
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Macrophage Colony-Stimulating Factor / physiology*
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Membrane Transport Proteins*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophils / drug effects
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Neutrophils / metabolism
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Neutrophils / pathology*
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Osteopetrosis / genetics
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Osteopetrosis / immunology
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Osteopetrosis / metabolism*
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RNA / analysis
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Necrosis Factor-alpha / biosynthesis*
Substances
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Antibodies, Blocking
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Bacterial Proteins
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Chemokine CXCL2
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Chemokines
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Cxcl2 protein, mouse
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DNA Primers
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Interleukin-1
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Interleukin-8
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Lipopolysaccharide Receptors
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Lipopolysaccharides
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Membrane Transport Proteins
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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msrA protein, Staphylococcus epidermidis
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RNA
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Macrophage Colony-Stimulating Factor