A new function for the calcineurin b subunit: antiplatelet aggregation and anticoagulation.

Calcineurin is the only Ca(2+) /calmodulin-dependent serine/threonine protein phosphatase. The roles of the cytosolic calcineurin have been well researched; however, the roles of the serum calcineurin remain unknown. Here, we report that the recombinant human calcineurin B subunit (CnB) can bind to rabbit platelets and show an antiplatelet aggregation activity. Furthermore, CnB exerts an anticoagulant effect by prolonging the activated partial thromboplastin time and thrombin time and reducing the plasma fibrinogen concentration in a dose-dependent manner. We further reveal that the functional domain associated with the anticoagulant activity of CnB is located in the C-terminus. Hemolysis test and intravenous stimulation study show that the recombinant CnB does not cause obvious hemolysis and is safe for intravenous injection. These results reveal a new function of calcineurin B subunit. They also give an explanation for the roles of calcineurin B subunit in serum and point to a possible implication in antithrombotic therapy.

[The therapeutic effect of soluble inducible costimulator fusion protein on inflammation in a murine model of allergic asthma].

OBJECTIVE: To examine the therapeutic effect of inducible costimulator fusion protein (ICOS-Ig) on airway inflammation in a murine model of allergic asthma. METHODS: Thirty-two healthy female BALB/c mice were randomly divided into four groups, namely the asthma group (group A), the ICOS-Ig treated group (group B), the control antibody group (group C), and the saline challenged group (group D), with 8 mice in each group. ICOS-Ig was produced by the eukaryotic expression technology. A murine model of allergic asthma was made by sensitizing animals with ovalbumin and exposing them to repeated ovalbumin inhalation challenges. After the mice were treated with ICOS-Ig at the time of ovalbumin challenge, the airway responsiveness, inflammatory cells and the cytokine content in bronchoalveolar lavage fluid (BALF), the level of IgE and Th1/Th2 in blood, and the lung histology were measured to observe the effect of the treatment on asthma in vivo. RESULTS: (1) FACS analysis confirmed that ICOS-Ig had the binding activity to B220 murine splenocytes. (2) Trans-pulmonary pressure change was significantly reduced in mice from group B [(33 +/- 12)%] compared with group A [(58 +/- 10)%, P < 0.01]. The total cell numbers of BALF in mice from group B [(5.9 +/- 3.1) x 10(7)/L] were decreased compared with group A [(22.6 +/- 5.3) x 10(7)/L, P < 0.01]. The percentage of eosinophils in BALF in mice from group B (0.020 +/- 0.020) was reduced significantly as compared with group A (0.070 +/- 0.030, P < 0.01). IL-4 content in BALF was reduced in mice from group B [(77 +/- 31)ng/L] compared with group A [(179 +/- 44) ng/L, P < 0.01]. IgE in blood was decreased in mice from group B [(175 +/- 33)microg/L] compared with group A [(282 +/- 22)microg/L, P < 0.01]. Th2 cell numbers in blood were reduced in mice from group B [(4.5 +/- 1.0)% ] compared with group A [(11.1 +/- 2.5)%, P < 0.01]. (3) Compared with group A, the pulmonary inflammation in group B was relieved and inflammatory changes in airway epithelium were absent. CONCLUSION: ICOS-Ig has an inhibitory effect on inflammation in a murine model of allergic asthma through the blockade of ICOS costimulatory pathway and decreases the level of IgE by altering differentiation of Th1/Th2 lymphocyte subsets in vivo.