Glucosaminylmuramyl dipeptide (GMDP) modulates endothelial cell activities in vitro but has no effect on angiogenesis in vivo.

Abstract

The aim of the study was to evaluate the effects of GMDP on angiogenesis in vivo and as a modulator of human umbilical vein endothelial cell proliferation, cell surface antigen expression and cell adhesion in vitro. Human umbilical vein endothelial cells (HUVEC), fertilized white leghorn chicken eggs, antibodies against adhesion molecules and glucosaminylmuramyl dipeptide (GMDP). GMDP [0.01-100 micrograms/ml] applied to cell cultures for 6-72 h and to the chick chorioallantoic membrane (CAM) for four days. Angiogenic activity of GMDP in vivo was assessed using the CAM assay; HUVEC proliferation was measured by tritiated thymidine incorporation and cell cycle studies; cell surface antigen expression by indirect immunofluorescence and flow cytometry; cell adhesion by quantification of [3H]-thymidine labeled leukocyte adherence to HUVEC monolayers. Statistical analysis was performed using one-way ANOVA and if necessary was followed by Duncan's multiple range test for variables. GMDP induced [3H]-thymidine incorporation in a concentration- and time-dependent manner (p < 0.003) and significantly increased the porportion of cells in the S phase of the cell cycle (p < 0.03). It weakly augmented the expression of ICAM-1 and CD31 but not adhesion of leukocytes to HUVEC monolayers GMDP was not angiogenic in the CAM assay. GMDP can modulate endothelial cell activity without the induction of angiogenesis in vivo which may have implications for its use as a therapeutic agent.