Leukocyte migration: dismantling inhibition

A new study demonstrates that the Src-family kinases Fgr and Hck inhibit chemokine signaling in polymorphonuclear leukocytes and dendritic cells by phosphorylation of PIR-B, an inhibitory receptor expressed on leukocytes. In resting cells, PIR-B phosphorylation is constitutive but is decreased transiently by addition of chemokines. In Fgr/Hck-deficient cells, constitutive PIR-B phosphorylation is markedly decreased. These Src-family kinases have a novel role in tonic inhibition of cell activation that must be overcome to allow the phenotypic effects of chemokine signaling through G-protein-coupled receptor ligands.     

系统性红斑狼疮合并隐球菌脑膜炎1例

1临床资料 患者女,42岁。因“反复关节痛、口腔溃疡4年,头痛10d”于2008年1月急诊入院,患者4a前因反复关节痛、口腔溃疡,当地医院查自身抗体：ANA（＋）,nRNP／Sm、SSA、组蛋白均阳性。血常规中白细胞2．4×10^9／L,红细胞3．42×10^12／L,血红蛋白73g/L。诊断为系统性红斑狼疮,给予强的松40mg／d口服1个月后病情好转,3a内逐渐将强的松减量为10mg／d维持已1a。     

Deoxyribonuclease-Inhibitory antibodies in systemic lupus erythematosus

Deoxyribonucleases (DNases) are key enzymes for digesting DNA. Abnormalities in the function of these enzymes may contribute to the development of anti-DNA antibodies in systemic lupus erythematosus (SLE). In this study, we used bovine DNase 1-coated ELISA plates to screen anti-DNase antibodies in SLE patients. About 62% of the sera of SLE patients (63/101) were positive for anti-DNase antibodies compared to only 8% of normal controls (8/98). A positive correlation was also found between the concentrations of anti-DNase and anti-DNA antibodies in sera of SLE patients. Affinity-purified anti-DNase immunoglobulin G (IgG) from pooled sera of SLE patients bound to bovine DNase as well as DNA. A synthetic peptide, corresponding to the catalytic site of DNase, was able to completely inhibit the binding of anti-DNase IgG to DNase. In addition to bovine DNase, the anti-DNase IgG also bound to and inhibited the enzymatic activities of DNase present in streptococcal supernatants and human urine. Immunization of lupus-prone NZB/NZW mice with bovine DNase enhanced the production of anti-DNase and DNA antibodies, and accelerated the occurrence of proteinuria. Taken together, these results suggest that DNase-inhibitory antibodies which recognize a conserved epitope near the catalytic site of DNase may act in the pathogenesis of SLE.