ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3.

Cellular adhesion plays important roles in a variety of biological processes. The ADAM family contains disintegrin-like and metalloproteinase-like domains which potentially have cell adhesion and protease activities. Recent studies suggest that the interaction between 14-3-3zeta and ADAM22cyt can regulate cell adhesion and spreading, therefore it has a potential role in neural development and function. 14-3-3 family has seven highly conserved members that regulate various cellular functions. Using yeast two-hybrid method, we identified that ADAM22cyt bound some other 14-3-3 family members. The interaction was further confirmed by in vitro protein pull-down assay and co-immunoprecipitation. We also found that the overexpression of exogenous ADAM22 in HEK293 cells could significantly enhance cell adhesion and spreading, compared with the truncated ADAM22 lack of 14-3-3 binding motifs. These results strongly demonstrated a functional role for ADAM22/14-3-3 in cell adhesion and spreading.

The CD28 peptidemimic can induce mixed chimerism and prolong the survival of cardiac allografts.

Costimulatory blockade with CD28 peptidemimic (CD28PM, CD28 PM was synthesized by solid phase synthetic methods) prolongs cardiac allograft survival in mice, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding B7 blockade to a chimerism inducing nonmyeloablative regimen in mice and observed a significant improvement of donor bone marrow cells (BMC) engraftment, which had been associated with mixed chimerism and long-term survival of cardiac allografts. The mixed lymphocyte reaction (MLR) and the ear pinna cardiac transplantation model were performed to evaluate the effects of CD28PM in induction of specific immune hypo-response and extension of allograft survival. The expressed rates of B7.1 and B7.2 on the C57BL/6 splenocytes were 56.25% and 20.52%, respectively. The specific hypo-response status was established after immunization with CD28PM pre-treated donor splenocytes and the average inhibition rate was only 43% compared with normal control. Subsequently, a total number of 2 x 10(7) bone marrow cells per mouse were implanted to the recipients. The allogenic chimerism was obviously observed with the rate as high as 8.84% (mean) at the time point of day 14. During the first 50 days post bone marrow transfusion (BMT) the chimerism rate declined stepwise. But from 50 to 100 days, the chimerism rate sustained in a range of 3.35% to 4.6%. The results of transplantation experiments showed the survival of allgenic cardiac grafts were maintained over 100 days in recipients. Thus, donor BMC engraftment with mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Mixed chimerism approach, by the addition of CD28-B7 costimulatory blockade with CD28PM, has been shown to establish mixed chimerism and induce cardiac allograft tolerance in mice.