Notch2 and Delta-like 1 (Dll1) have been implicated in the development of marginal zone B (MZB) cells. In the present study, we characterized the expression and function of mouse Notch receptors and ligands in the spleen by using newly generated mAbs. Although Notch2 was expressed on both B and T cells in the spleen, the highest expression was observed on precursors of marginal zone B and MZB cells. Dll1 was expressed on macrophage and erythroblasts in the red pulp, but not on B cells or marginal zone macrophage. Administration of a blocking mAb against Dll1 not only blocked the development of MZB cells in juvenile mice but also gradually depleted the pre-established MZB cells in adult mice, indicating a critical role for Dll1 in the maintenance of MZB cells in the spleen of normal mice. Interestingly, Dll1 was not necessary for the maintenance of MZB cells in lupus-prone (NZB x NZW) F1 mice particularly after the onset of the disease, suggesting that the Dll1 independence may be a feature of dysregulated MZB cells producing auto-antibodies.

No abstract

No abstract

The importance of Notch signaling to maintain CD8- dendritic cells (DCs) in the spleen has recently been revealed. However, the ligand responsible for this Notch signaling has not been determined yet. In this study, we demonstrated that blocking of Delta-like (Dll) 1 alone had no significant effect on the maintenance of CD8- DCs while marginal zone (MZ) B cells were significantly reduced in the spleen of mice. On the other hand, blocking of Dll1, Dll4, Jagged1 and Jagged2 significantly decreased CD8- DCs. All these Notch ligands are expressed predominantly in the red pulp of the spleen where CD8- DCs reside. These results indicate a differential regulation of CD8- DCs and MZ B cells by Notch ligands in the spleen.

Background:LacCer is known to regulate PLA 2 activity in cells, but the precise mechanisms have not been elucidated. Results: LacCer binds to cPLA 2 ␣ and increases its enzymatic activity. Conclusion: LacCer is identified as a novel and direct activator of cPLA 2 ␣. Significance: This research provides new insights into the regulatory mechanisms of cPLA 2 ␣ and the physiological functions of LacCer as a signaling molecule.

No abstract

No abstract

This study showed that nitric oxide (NO)-generating S-nitrosothiols, S-nitroso-Nacetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO), increased proliferation of BALB/c 3T3 (clone A31-1-1) fibroblasts in vitro. Treatment with SNAP at a relatively low concentration (0.005-0.02 raM) induced an increase in cell number compared to control. SNAP (0.005-0.02 raM) and GSNO (0.025-0.05 raM) both showed an increase of [3H]thymidine incorporation in exponentially growing cells in a dose-dependent manner. The maximal effect was observed at about 40 and 90% above control at 0.02 mM and 0.05 raM, respectively. The increase induced by 0.02 mM SNAP was abolished by the addition of 0.01mM oxyhemoglobin, a scavenger of NO.[3H]Thymidine incorporation in stationary cells was also increased by SNAP. In addition, 0.02raM SNAP produced a 1.8-3.2-fold increase of thymidine kinase activity in exponentially growing cells.