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Primary Bone (primary + bone)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Distinct contributions of different CD40 TRAF binding sites to CD154-induced dendritic cell maturation and IL-12 secretion

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003
Matthew
Abstract The mechanisms by which CD40 controls the maturation and antigen presentation functions of dendritic cells (DC) remains largely undefined in this critical cell type. To examine this question, we have employed retroviral transduction of primary bone marrow-derived mouse DC. Mutation of the distinct binding sites for TNF receptor-associated factor 6 (TRAF6) and for TRAF 2, 3, and 5 in the CD40 cytoplasmic domain revealed their independent contributions to DC maturation and activation of NF-,B. In contrast, disruption of the TRAF6 but not the TRAF 2,3,5 binding site markedly decreased IL-12 p40 secretion along with p38 and JNK activation in response to CD154 stimulation. These data document a clear bifurcation of the CD40 signaling cascade in primary DC at the level of thereceptor's two distinct and autonomous TRAF binding sites, and reveal the predominant role of the TRAF6 binding site in CD40-induced pro-inflammatory cytokine production by these cells. [source]

CpG and LPS can interfere negatively with prion clearance in macrophage and microglial cells

FEBS JOURNAL, Issue 22 2007
Sabine Gilch
Cells of the innate immune system play important roles in the progression of prion disease after peripheral infection. It has been found in vivo and in vitro that the expression of the cellular prion protein (PrPc) is up-regulated on stimulation of immune cells, also indicating the functional importance of PrPc in the immune system. The aim of our study was to investigate the impact of cytosine-phosphate-guanosine- and lipopolysaccharide-induced PrPc up-regulation on the uptake and processing of the pathological prion protein (PrPSc) in phagocytic innate immune cells. For this purpose, we challenged the macrophage cell line J774, the microglial cell line BV-2 and primary bone marrow-derived macrophages in a resting or stimulated state with various prion strains, and monitored the uptake and clearance of PrPSc. Interestingly, stimulation led either to a transient increase in the level of PrPSc relative to unstimulated cells or to a decelerated degradation of PrPSc. These features were dependent on cell type and prion strain. Our data indicate that the stimulation of innate immune cells may be able to support transient prion propagation, possibly explained by an increased PrPc cell surface expression in stimulated cells. We suggest that stimulation of innate immune cells can lead to an imbalance between the propagation and degradation of PrPSc. [source]

Osteoclastogenesis-Related Antigen, a Novel Molecule on Mouse Stromal Cells, Regulates Osteoclastogenesis,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2003
Satoshi Arai
Abstract Osteoclastogenesis is regulated by RANKL expressed on stromal cells. In this study, we sought to isolate a new surface molecule regulating osteoclastogenesis on stromal cells by generating monoclonal antibodies. A rat was immunized with the mouse stromal cell line, TSB13, which can support osteoclastogenesis, and a monoclonal antibody, A15-1, was obtained. A15-1 bound to a surface antigen on TSB13 cells, termed osteoclastogenesis-related antigen (OCRA), and immunoprecipitation with this antibody revealed that OCRA was a 220-kDa molecule. By means of flow cytometry, the A15-1 antigen (OCRA) was found to be expressed on various mesenchymal cell lines but not on hematopoietic cell lines, and the expression level of OCRA on the TSB13 cells was slightly increased by treatment with 1,,25(OH)2D3. When osteoclast progenitors and TSB13 cells were co-cultured in the presence of 1,,25(OH)2D3, the addition of A15-1 inhibited osteoclast differentiation in a dose-dependent manner; however, no significant inhibition of soluble RANKL-induced osteoclastogenesis was observed, suggesting that A15-1 inhibited only stromal cell-dependent osteoclastogenesis. The same inhibitory effect of A15-1 was also observed when primary bone marrow-derived stromal cells were used. The osteoclastogenesis-promoting effects of other osteotropic factors, such as parathyroid hormone (PTH) and interleukin (IL)-1,, were also inhibited by A15-1. Time-course analysis of osteoclast differentiation in vitro indicated that the initial 2 days of treatment with A15-1 was sufficient for inhibition, suggesting that A15-1 inhibits the early stages of osteoclast differentiation. Finally, we investigated the in vivo effects of A15-1 on PTH-induced hypercalcemia in mice. Treatment with A15-1 significantly decreased the osteoclast surface in the PTH-administered mice. Taken together, our data indicate that OCRA, a novel A15-1-detected antigen, regulates stromal cell-dependent osteoclastogenesis. [source]

Two peculiar conditions following a coma: A clinical case of heterotopic ossification concomitant with keloid formation

CLINICAL ANATOMY, Issue 4 2008
Carla Palumbo
Abstract The etiology and formation pattern of heterotopic ossifications (HO) are still unknown. They occur in soft tissues in which bone does not normally form, near one or more proximal joints. In this article, the authors report a peculiar case of a 31-year-old patient affected by scapulo-humeral ankylosis that occurred about 6 months after a coma, in which two unusual concomitant conditions were observed: HO formation in the scapulo-humeral region and the development of keloids during wound repair. The scapulo-humeral ankylosis was resolved surgically with the removal of the HO, which was then studied morphologically to understand its formation pattern. By light microscopy and transmission electron microscopy, it was observed that heterotopic bone displays the normal microscopic structure of primary bone, in which two types of bone tissue were recognized, i.e., woven-fibered bone, deeply located and produced first, and lamellar bone. This suggests that the pattern of HO formation retraces the ontogenetic steps that normally occur during intramembranous ossification. The authors also discuss the peculiar concomitance of HO formation and keloid development, speculating that, although they are different conditions localized in dissimilar regions, they might be hypothetically triggered by a common event, such as the release of factors likely issued during the coma status. Clin. Anat. 21:348,354, 2008. © 2008 Wiley-Liss, Inc. [source]