Investigating the role of histamine type 2 receptors in the occurrence of aplastic anemia derived from immunity

Abstract

Abstract A great deal of data showed that disorders of cytokines, mainly produced by lymphocytes, played great roles in the development of AA. Some researchers found Histamine-2 receptor (H 2 R) existing on the lymphocytes and had some connection with the production of cytokines. Here, we made AA mice model by transfusion of lymphocytes from H-2 match but M1s unmatch strain DBA/2 to sublethally radiated Balb/c mice. Nine to 14 days after the injection, most of the mice suffered from deadly AA. Splenocytes from AA mice can inhibit the formation of normal BM CFU-GM to 52.3 ± 19%, but those of radiated mice had no inhibition. It is interesting that 10 −5 M cimetidine, an H 2 -R antagonist, could block the inhibition completely. Further ELISA results suggested that lymphocytes from AA model mice secreted higher levels of IFN-γ and TNF-α than radiated and/or normal mice after induced with PHA and LPS respectively. Again, when incubated with 10 −5 M cimetidine, the concentration of IFNγ and TNFα were both back to normal mice. RT-PCR revealed that bone marrow cells of AA model expressed higher level of FAS and iNOS mRNA, whereas low expression of FAS and no iNOS mRNA were found in normal mice. On the other hand, lymphocytes from AA mice model expressed FAS-Ligand, compared with none in normal mice. We think that high levels of negative factors TNF-α and INF-γ, produced by activated lymphocytes, is one of the reason the AA occurred in immune-induced model H 2 -R antagonist could reduce their production in vitro. In addition, apoptosis of HSC/HPC caused by the ligation of FAS-L and FAS is another important factor.