MURAMYL PEPTIDES AUGMENT THE IN-VITRO AND IN-VIVO CYTOSTATIC ACTIVITYOF CANINE PLASTIC-ADHERENT MONONUCLEAR-CELLS AGAINST CANINE OSTEOSARCOMA CELLS

A tumor cytostasis assay was developed that measured the effect of the immunomodulator muramyl dipeptide (MDP) on the in vitro cytostatic ac tivity 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 pop ulation was characterized by cell morphology, non-specific esterase st aining, and flow microfluorometry to be approximately 42% monocytes, 4 9% lymphocytes, and 8% eosinophils. Canine plastic-adherent mononuclea r cells spontaneously caused cytostasis of D-17 canine osteosarcoma ta rget cell proliferation. The spontaneous cytostatic activity of adhere nt mononuclear cells was significantly augmented by exposure to MDP or to lipopolysaccharide (LPS), with maximal cytostatic activity being o bserved after combined exposure to MDP and LPS. Mononuclear cell cytos tasis toward D-17 canine osteosarcoma and A375 human melanoma cells wa s enhanced (P<0.05) when normal dogs were administered liposome-encaps ulated muramyl tripeptide phosphatidylethanolamine, a lipophilic deriv ative of MDP, by intravenous injection.