Induced And Constitutive Expression Of The P47 Resistance GTPases In The Mouse

It has generally been accepted that is in vertebrates immune system classically consist of two classical levels, namely innate immunity and adaptive immunity, both of which mainly make use of highly specialized cells-immune cell (largely leukocytes) to achieve the protection of organism bodies. Recently however increasing evidence indicates the existence of another level of immunity-cell autonomous immunity, namely normal body cells also can protect themselves by mounting sophisticated antipathogen states via the mediation of cytokines. Several such cell autonomous mechanisms induced by IFN have been characterized, among which is P47 GTPase family. P47 GTPases, a gene family including 22 members in mouse, are GTPases, characterized by the capability of being massively induced by IFN-gamma and considered to be cell autonomous resistant factors, whose resistant function and exact mechanism howeverremains vague.This work is mainly concerned with one family member IIGP-1(also a bit on IGTP) on organism level, and the results are listed below. Firstly significant IIGP-1 expression was detected in some of the hair follicles in the skin of WT mice. Further experiments on other tissues disclosed that IIGP-1, the expression of which was formerly considered as the result of sole IFN induction, is expressed in nearly most of the WT healthy mice tissues, especially intensively in liver. By screening IFN receptor targeted mice, this expression was found to be principally IFN (both type I and II) independent in some tissues e.g.in liver, heart and largely IFN dependent in others e.g. in skin and spleen. Finally the infection experiment on both WT and IFN-gamma receptor KO mice showed that 24-hours Listeria monocytogenes infected liver has around 10 fold more mRNA and 3 fold more protein expression of IIGP-1 than the basal expression level in uninfected WT liver and this increment is totally IFN-gamma dependent.This study, which disclosed for the first time the existence of constitutive expression of P47 GTPases in various healthy mouse tissues and the independency of this expression to IFN in some tissues (e.g.liver and heart), reformed our former understanding that IFN is the only mediator of P47GTPases expression, hence provided a drastically modified background against which function and mechanism exploration of these GTPases should be proceeded.