1.Blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergic state
Yong CAI ; Peijun ZHOU ; Shanzhong ZHANG
Chinese Journal of Organ Transplantation 2003;0(05):-
Objective To investigate the possibility of inducing anergy by blocking the CD40/CD154 and B7/CD28 costimulatory pathways and the reversal condition of anergic cells. Methods Splenocyte proliferation in primary mixed lymphocyte reaction (MLR) consisting of BALB/c as responder and C3H as stimulator was measured by the addition of different levels of anti-CD154 and anti-CD80 monocolonal antibody (mAb). To test the reversal condition of anergic cells induced by combined anti-CD154 and anti-CD80 mAbs blocking, C3H or C57BL/6J spleenocytes were irradiated, or different concentrations of recombinant mouse interleukin-2 (rmIL-2), or both C3H splenocytes and rmIL-2 were added to the anergic cells. Results The proliferation of anergic cells treated with both mAbs in the primary MLR was strongly inhibited in a dose-dependent manner. The cells proliferated in response to third party (C57BL/6J) stimulator. The cells did not respond to original (C3H) stimulator, and they also failed to proliferated in response to the addition of exogenous IL-2. Furthermore, the anergic state was reversed by both original (C3H) stimulator and the addition of exogenous rmIL-2. Conclusion The blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergy, and the anergic state can be reversed by both antigen restimulation and the addition of exogenous IL-2.
2.Tracking transplanted pancreatic islet cells in rats using magnetic resonance imaging
Bijing ZHOU ; Huijin HE ; Xiaoyuan FENG ; Shanzhong ZHANG ; Yanmei YANG
Fudan University Journal of Medical Sciences 2009;36(6):670-674
Objective To track superparamagnetic iron oxide (SPIO)-labeled pancreatic islet cells in rats using 3.0T magnetic resonance imaging (MRI), and to detect the survival and rejection of grafts after transplantation. Methods Twenty male Wistar rats and 5 male Lewis rats were included in the study. SPIO-labeled pancreatic islet cells were tracked using a GE 3.0T Signa Excite MRI scanner with an animal coil. The images of SPIO-labeled islet cells in rats after transplantation were compared with those of the unlabeled ones. FSE T2WI sequence and GRE T2*WI sequence were used for the detection. The sensitivity of images for detection of grafts was also compared. SPIO-labeled pancreatic islet cells isolated from Wistar and Lewis rats were transplanted into the liver of Wistar rats. Afterwards, the survival and rejection of islet cells were observed sequentially in these two growps. The rats in the syngeneic group were sacrificed 3 months post-transplantation, while the rats in the allogeneic group were sacrificed 3 weeks post-transplantation. MRI of the grafts were correlated with the pathological results. Results SPIO-labeled pancreatic islet cells were seen on MRI as distinct homogenous, hypointense spots in the liver. GRE T2*WI were more sensitive to the detection of SPIO-labeled islet cells than FSE T2WI. The relative count of hypointense spots in the syngeneic group were (90.03±9.52)%, (92.87±18.21)% and (86.25±24.81)%, respectively at 1 week, 2 weeks and 3 weeks after transplantation, while the relative count in the allogeneic group were (41.40±15.41)%, (33.41±14.01)% and (23.58±16.78)%, respectively. The difference between these counts was statistically significant (P<0.01). Iron particles were detected only in the SPIO-labeled cells. Three months post-transplantation, the grafts were found well-preserved in the liver of the rats of the syngeneic group, while only a few grafts were found in that of the allogeneic group. Conclusions MRI can be used to track SPIO-labeled islet cells in vivo, and has significant value in detecting the survival and rejection of grafts after transplantation in rats.
3.The prevalence of metabolic syndrome in Heilongjiang residents aged 20-74 years
Nannan WU ; Qiang LI ; Kaiting CHEN ; Yan FENG ; Xiaoying LIU ; Shanzhong LI ; Jinchao ZHANG
Chinese Journal of Endocrinology and Metabolism 2010;26(9):758-761
A cross-sectional study was conducted in Heilongjiang in a representative sample of 2 875Chinese adults aged from 20 to 74 years. Questionnaire was conducted. Their height, weight, waist circumference,blood pressure, blood glucose, serum insulin, lipids, and other indexes were determined. The criterion of International Diabetes Federation was applied for metabolic syndrome (MS) diagnosis. The results showed that the preliminary prevalence rate of MS was 19.34% and the age-adjusted prevalence rate of MS was 21.92% ( male 20.41% , female 23.11% ). The prevalence rate of MS increased with the age. The prevalence rate in the urban area was higher than that in the town and rural area ( both P < 0.05 ). The result of multiple factor logistic regression analysis showed that body fat content, insulin resistance, age, residential difference, drinking habit,daily staple food quantity, urine albumin, education, family history of obesity, and gender were related with MS.
4.Feature changes of MMP-2/9 activities and TIMP-1/2 protein expressions during the progression of pulmonary fibrosis in rats
Shanzhong TAN ; Chenghai LIU ; Wei ZHANG ; Xiong LU ; Weicheng YE ; Zhenzhen CAI ; Ping LIU
Journal of Integrative Medicine 2006;4(4):402-7
OBJECTIVE: To investigate the dynamic trends of activities of matrix metalloproteinase (MMP)-2/9 and protein expressions of their inhibitors-tissue inhibitor of matrix metalloproteinase (TIMP)-1/2 during the progression of pulmonary fibrosis in rats so as to get insight of the roles played by MMP-2/9 in lung injury and fibrogenesis. METHODS: Forty-eight SD rats were randomly divided into normal control group (n=18) and bleomycin (BLM)-treated group (n=30). The pulmonary fibrosis was induced by intratracheal injection of BLM once. At the consecutive time of 1 day, 3 days, 1 week, 2, 3, and 4 weeks after intoxication, the lung-to-body weight ratio was calculated and the inflammation and collagen deposition in lung tissue were checked by HE and Masson stainings respectively. Meanwhile, the content of hypdroxyproline (Hyp) in lung tissue was assayed with Jamall's method, the protein expressions of MMP-2/9, TIMP-1/2 were examined by Western blotting, and the activities of MMP-2/9 were detected by gelatin zymography. RESULTS: The histopathological changes in lung tissue in the BLM-treated group from 1 day to 2 weeks after intoxication presented local lesions, broadened alveolar wall and septum, infiltration with lots of inflammatory cells and few of fibroblasts inside alveolar space and septum. At this early stage in the BLM-treated group, the lung-to-body weight ratio was increased significantly, the protein expressions and activities of MMP-2/9 were obviously increased especially for activity of active MMP-2, and the protein expressions of TIMP-1/2 were also increased gradually, as compared with those in the normal control group. From 3 to 4 weeks after intoxication in the BLM-treated group, the alveolar structure was damaged, parts of the alveolar space collapsed and replaced by collagens and fibroblasts, and the alveolar wall and septum obviously widened with remarkable fibrotic characteristics, as compared with those in the normal control group. Meanwhile, the lung-to-body weight ratio and the activities of MMP-2/9 were decreased in the BLM-treated group as compared with those in the same group at 2 weeks after intoxication, but the content of Hyp and the protein expressions of TIMP-1/2 were both increased dramatically, especially at 4 weeks after intoxication. CONCLUSIONS: During the lung fibrogenesis induced by BLM in rats, the alveolar inflammation is the most important alteration with enhanced MMP-2/9 activities in the early stage. While in the late stage, the main change is displayed as pulmonary fibrosis, characterized by increased TIMP-1/2 and declined MMP-2/9 activities.