Effect of CCK-8 on the B7.1 and B7.2 expressions and costimulation of endotoxemia murine perineral macrophages

AIM: To investigate in vivo effects of CCK-8 on the expressions of B7.1 and B7.2 and the costimulatory activity for T lymphocytes in endotoxemia murine perineral macrophages.METHODS: BALB/c mice were randomly assigned to 8 groups (n=4) injected ip.with NS alone (0.2-0.3 mL/mouse),or with LPS (100 μg/mouse),in the presence or absence of CCK-8 (5 nmol/mouse) and CR1409 (100 μg/mouse),CR2945 (100 μg/mouse).After 12 h,macrophages were purified from the peritoneal exudate.The B7.1/B7.2 expression on purified macrophages was analyzed by flow cytometry and,alternatively,purified macrophages were assayed for macrophage costimulatory activity.ConA was added into the culture medium to stimulate CD4+T cell proliferation.The proliferation was determined by measuring ［³H］-TdR incorporation in a β-scintillation counter.RESULTS: The in vivo administration of CCK-8 resulted in increase of B7.2 expression,but without any influence on B7.1 expression in peritoneal macrophages.CCK-8 also exhibited increased the ［³H］-TdR incorporation in CD4+T cells.However,the in vivo CCK-8 administration reduced both B7.1 and B7.2 expression in LPS-induced endotoxemia murine peritoneal macrophages and the ［³H］-TdR incorporation in CD4+T cells.These effects were consistent with the in vitro effects of CCK-8 on LPS-stimulated peripheral macrophages.CR1409 and CR2945 abolished the above effects of CCK-8.CR1409 was more effective than CR2945.CONCLUSION: CCK-8 enhances macrophage costimulatory activity by upregulating B7.2 expression,and at the same time,reduces LPS-induced costimulatory activity of endotoxemia murine perineral macrophages by downregulating B7.1 and B7.2 expression,which is mediated by CCK1R and CCK2R.CCK1R might be the major receptor responsible for the modulation of CCK-8 on costimulation.