Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice.
OBJECTIVE
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.
Jiang
S
S
Second Department of Pathology, Niigata University School of Medicine, Japan.
Naito
M
M
Kaizu
C
C
Kuwata
K
K
Hasegawa
G
G
Mukaida
N
N
Shultz
L D
LD
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis*; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D007375:Interleukin-1 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000276:immunology; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010022:Osteopetrosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D019138:Antibodies, Blocking; D001426:Bacterial Proteins; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D017931:DNA Primers; D007375:Interleukin-1; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C066202:msrA protein, Staphylococcus epidermidis; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor