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

Abstract.

Objective and Design: 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.¶Materials: Human umbilical vein endothelial cells (HUVEC), fertilized white leghorn chicken eggs, antibodies against adhesion molecules and glucosaminylmuramyl dipeptide (GMDP).¶Treatment: GMDP [0.01–100 μg/ml] applied to cell cultures for 6–72 h and to the chick chorioallantoic membrane (CAM) for four days.¶Methods: 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.¶Results: GMDP induced [³H]-thymidine incorporation in a concentration- and time-dependent manner (p < 0.003) and significantly increased the proportion 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.¶Conclusions: GMDP can modulate endothelial cell activity without the induction of angiogenesis in vivo which may have implications for its use as a therapeutic agent.