Muramyl Peptides Augment the In Vitro and In Vivo Cytostatic Activity of Canine Plastic-Adherent Mononuclear Cells Against Canine Osteosarcoma Cells

Abstract

A tumor cytostasis assay was developed that measured the effect of the immunomodulator muramyl dipeptide (MDP) on the in vitro cytostatic activity of canine plastic-adherent mononuclear cells. Mononuclear cells were isolated from the peripheral blood of healthy Beagle donors and allowed to adhere to a 96-well microtiter plate. The adherent cell population was characterized by cell morphology, non-specific esterase staining, and flow microfluorometry to be approximately 42% monocytes, 49% lymphocytes, and 8% eosinophils.

Canine plastic-adherent mononuclear cells spontaneously caused cytostasis of D-17 canine osteosarcoma target cell proliferation. The spontaneous cytostatic activity of adherent mononuclear cells was significantly augmented by exposure to MDP or to lipopolysaccharide (LPS), with maximal cytostatic activity being observed after combined exposure to MDP and LPS.

Mononuclear cell cytostasis toward D-17 canine osteosarcoma and A375 human melanoma cells was enhanced (P<0.05) when normal dogs were administered liposome-encapsulated muramyl tripeptide phosphatidylethanolamine, a lipophilic derivative of MDP, by intravenous injection.