[A case of pulmonary inflammatory pseudotumor with hypergammaglobulinemia, elevated ANA, and uveitis].

A 63-year-old man presented with a chronic myeloproliferative disorder complicated with left pneumonia. His pneumonia was cured with antibiotics, but a nodular lesion remained in his chest radiographs together with hypergammaglobulinemia, a high titer of anti-nuclear antigen, and uveitis with secondary glaucoma. Specimens obtained by transbronchial lung biopsy showed a mixed accumulation of plasma cells, lymphocytes, and histiocytes as well as a spindle cell proliferation diagnosed as pulmonary inflammatory pseudotumor. The specimen did not show any recombination indicative of a heavy or a light chain of immunoglobulin in Southern blotting analysis. Oral prednisolone treatment improved the pulmonary nodular lesion, the abnormal laboratory data, and the uveitis. These findings suggest that much of the gammaglobulin produced by plasma cells in the inflammatory pseudotumor caused a variety of clinical symptoms.

Defective macrophage recruitment and clearance of apoptotic cells in the uterus of osteopetrotic mutant mice lacking macrophage colony-stimulating factor (M-CSF).

There are large numbers of macrophages in the uterus of normal mice. During estrus and metestrus endometrial epithelial cells express macrophage colony-stimulating factor (M-CSF). Numbers of uterine macrophages showed cyclic changes and accumulated beneath the endometrial epithelial cells at estrus and metestrus. However, numbers of uterine macrophages in osteopetrotic (op/op) mice were reduced tenfold compared with normal littermate mice and op/op mouse macrophages were ultrastructurally immature throughout the estrous cycle. Several macrophage chemokines were produced in the uterus. However, administration of antibody against the macrophage colony stimulating factor receptor (c-fms) severely diminished the number of uterine macrophages in normal littermate mice, implying that M-CSF plays a major role in macrophage recruitment in the uterus. Endometrial epithelial cells underwent apoptosis at estrus and metestrus and were disposed into the uterine lumen in op/op mice and littermate mice. In littermate mice a large number of macrophages accumulated beneath the endometrial epithelial cells and actively removed apoptotic cells. In contrast, there were few macrophages in op/op mice and clearance of apoptotic cells by macrophages was defective in the uterus of these mice. Thus M-CSF plays important roles in the recruitment and differentiation of macrophages and in scavenging effete epithelial cells in the uterus.

Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor.

Macrophage-colony-stimulating factor (M-CSF) regulates the survival, proliferation and differentiation of the mononuclear phagocyte lineage. Osteopetrotic (op/op) mice defective in producing functional M-CSF were used in order to investigate the role of M-CSF on the development of microglia and brain macrophages and the expression of scavenger receptor (SR). Adult op/op and littermate mice at 10-47 weeks of age were investigated by immunohistochemistry with a panel of monoclonal antibodies (F4/80, Mac-1, anti-major histocompatibility complex (MHC) class II and anti-SR), electron microscopy and reverse transcriptase-polymerase chain reaction (RT-PCR). Microglia were weakly immunolabeled with F4/80 and Mac-1 in op/op and littermate mice, but the number of microglia in op/op mice was reduced in the cerebrum, cerebellum and brainstem compared with that of normal littermates. The numbers of Mac-1-positive microglia in op/op mice was 39% (pons) and 30% (cerebellar cortex) lower than that in normal littermates (P<0.05). In addition, the microglia cell processes in op/op mice were often shorter than those in control mice. In op/op and littermate mice, both MHC class II and SR were present in perivascular cells and macrophages of the leptomeninx and choroid plexus. Ultrastructurally, perivascular cells appeared to be immature, since their cytoplasm was narrow and contained few inclusion bodies compared with those of control mice. Reverse transcriptase-polymerase chain reaction showed a weak expression for SR mRNA in the brains of op/op mice as well as littermate mice. These results indicate that microglia are partly dependent on M-CSF for their proliferation and differentiation and that M-CSF has no significant effect on the expression of SR in the physiological brain. The study also suggests that M-CSF affects the maturation of perivascular cells at the ultrastructural level.

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

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.