The Changes Of Peritoneal Macrophage B7-1 And B7-2 Expressions In The Rat Chronic Mild Stress Model Of Depression

Objective: Depression (DEP) is a complex mood disorder, with the main clinical feature of depressed mood sustaining, which is a common stress-induced disease. Being in stress, sympathetic nervous system is activated. Both peripheral sympa- thetic nerves and adrenal medulla release neurontransmitters, following by significantly increased blood catecholamines (CA, including epinephrine (E) and norepinephrine (NE)). The sympa- thetic nerve regulates the immune system not only by changing the blood flow conditions and its internal microenvironment in lymphoid organs, but also by directly acting on the lymphocytes and regulating the immune cells functions through adrenergic receptors (AR) on the surface of immune cells. There are two kinds of adrenergic receptors,αandβ-AR. Bothα₂-AR andβ₂-AR exist on the cell membrane of macrophages. Activing theβ₂-AR on the cell membrane of macrophages will restrain the activity of macrophages, contranrily activing theα₂-AR will strengthen it. Some researchers have proved that the mononu- clearphagocytes were actived in depresssive patients. Activated macrophage can initiate the acquired immune responses as a antigen presenting cell. Then T lymphocytes become activated, proliferated and then differentiated into effective lymphocytes, induced by activated macrophages. As costimulatory molecules, both B7-1 and B7-2 on the cell membrane of macrophages appear to be equivalent in the costimulation of T cell prolife- ration. However, B7-1 and B7-2 may differ in the signals provided for T cell differentiantion, with B7-2 favoring Th2 development. So the expressions of B7-1 and B7-2 on the cell membrane of macrophages play a important role on keeping the balance between Th1 cells and Th2 cells. Some researchers have proved that Th1 cells and Th2 cells are out of balance in depressive patients. However, there is still few reports about the effects ofcatecholamines, released by sympathetic adrenal medulla system, on regulating B7-1 and B7-2 expressions through adrenaline receptors on the cell membrane of peritoneal macrophages, and then participating in Th1 cells and Th2 cells imbalance in depression. we will investigate the changes of peritoneal macrphages B7-1 and B7-2 expressions both in the rat chronic mild stress model of depression and in vitro affected by adrenaline and adrenoceptor antagonists, in order to supply some new ideas for the pathgenesis of depression; to provide some clues for the intervening mechanism of physical diseases caused by psychosocial factors and to provide some scientific evidences for spiritual damages compensation in compensation medicine.Methods 1:Twenty-five healthy Wistar rats were randomly divided into 5 groups: control group,depression group,propra- nolol (β-adrenoceptor antagonist) group,phentolamine (α- adre- noceptor antagonist) group and imipramine (depression medica- tion) group, five in each group. The chronic unpredictable mild stress(CUMS) model was adopted to stimulate depression in humans. Propranolol or phentolamine or imipramine pretreat- ment was used as an anti-stress factor. On the first day and the last day of eight weeks experiment, all the rates` open field activities and body weights were investigated, and the B7-1 and B7-2 expressions of rat peritoneal macrophages were analyzed by flow cytometry.Methods 2: The rat peritoneal macrophages were treated with 10,100μmol/L adrenaline respectively for 24h in vitro, then peritoneal macrophages were incubated with 0.1,1,10μmol/L propranolol,phentolamine and imipramine separately. 24h later, the cells were collected and examined the expressions of B7-1 and B7-2 on peritoneal macrophages by flow cytometer.Results:The data were presented as Mean±SD and analyzed with ANOVA and least significant difference (LSD) using SPSS 11.5 statistical program. A level of P<0.05 was considered as statistical significance.(1) The results of the open field testâ‘ Comparing with the control group, all of groups had no significant changes on the first day of the experiment.â‘¡On the last day of the experiment, comparing with the control group (Crossing score 83.00±21.39, Rearing score 17.60±2.30), the open field activities of the depression (Crossing score 31.80±19.00, Rearing score 3.20±2.28) and propranolol group (Crossing score 47.20±9.09, Rearing score 3.40±2.07) both had signifycant depressive changes, but phentolamine group (Crossing score 72.80±15.55, Rearing score 16.80±7.19) and imipramine group (Crossing score 83.20±10.16, Rearing score 15.80±4.26) had no significant depressive changes.â‘¢On the last day of the experiment,comparing with the depression group, both phentolamine group and imipramine group had significant depressive changes.(2)The results of the body weightsâ‘ Comparing with the control group, all of groups had no significant changes on the first day of the experiment.â‘¡On the last day of the experiment, comparing with the control group (286.86±41.96g), the weights of the depression (241.60±33.93g) and propranolol group (242.36±27.47g) both had significant depressive changes, but phentolamine group (267.04±30.86g) and imipramine group (245.72±27.16g) had no significant depressive changes.(3) The change of peritoneal macrophages B7-1 expression in the rat chronic mild stress model of depressionBoth the depression and propranolol group had significant decreese of peritoneal macrophages B7-1 expression, comparing with the control group. And that of the phentolamine group and imipramine group had significant increasive changes than the depression group.(4) The change of peritoneal macrophages B7-2 expression in the rat chronic mild stress model of depressionBoth the depression and propranolol groups had significant increasive changes of peritoneal macrophages B7-2 expression than the control group. Comparing with the depress group, the propranolol group had a significant increasive change, but both phentolamine group and imipramine group had significant depressive changes.(5) The effect of adrenaline and adrenoceptor antagonists on regulating peritoneal macrophages B7-1 and B7-2 expressions in vitroâ‘ Comparing with the control group, adrenaline group,propranolol groups,phentolamine groups and imipramine groups all had no significant changes of peritoneal macrophages B7-1 expression.â‘¡Comparing with the control group, 10μmol/L adrenaline group and 10μmol/L propranolol group had significant increase of peritoneal macrophages B7-2 expression. Comparing with the 10μmol/L adrenaline group, 0.1,1μmol/L propranolol group had a significant depressive expression, but 10μmol/L propranolol group had a significant increased expression.â‘¢Comparing with the control group, 10μmol/L adrenaline group had a significant increase peritoneal macrophages B7-2 expression. 0.1,1,10μmol/L phentolamine groups all had a significant decrease of peritoneal macrophages B7-2 expression to be compared with the 10μmol/L adrenaline group.â‘£Comparing with the control group, peritoneal macrophages B7-2 expression were significant increased with the effect of 10μmol/L adrenaline. 0.1,1,10μmol/L imipramine groups all had significant decreased expression to be compared with the 10μmol/L adrenaline group.⑤Comparing with the control group, 100μmol/L adrenaline group had a significant increase peritoneal macrophages B7-2 expression. Comparing with the 100μmol/L adrenaline group, 0.1,1,10μmol/L propranolol groups all had a significant increased expression.â‘¥Comparing with the control group, 100μmol/L adrenaline group and 0.1μmol/L phentolamine group had a significant increase peritoneal macrophages B7-2 expression. 0.1μmol/L phentolamine group had a significant increase expression but 1,10μmol/L phentolamine groups had a significant decreased expression to be compared with the 100μmol/L adrenaline group.⑦Comparing with the control group, 100μmol/L adrenaline group had a significant increase peritoneal macrophages B7-2 expression. Comparing with the 100μmol/L adrenaline group, 0.1,1,10μmol/L imipramine groups all had significant decreasive changes.Conclusions: To a certain degree, the present study comfired that sympathetic adrenal medulla system may be participate in the immune systemic changes by upregulating peritoneal macrophages B7-2 expression throughα2-adrenoceptor both in the process of the development of depression and in vitro.