interleukin-8 and Osteopetrosis

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.. 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.. 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.. 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.

Topics: Animals; Antibodies, Blocking; Bacterial Proteins; Chemokine CXCL2; Chemokines; DNA Primers; Fluorescent Antibody Technique, Indirect; Interleukin-1; Interleukin-8; Kupffer Cells; Lipopolysaccharide Receptors; Lipopolysaccharides; Liver; Lymphocyte Activation; Macrophage Colony-Stimulating Factor; Membrane Transport Proteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Osteopetrosis; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Tumor Necrosis Factor-alpha