Biochemical and functional studies of the activation of tumoricidal properties in macrophages by muramyl peptides
The systemic injection of muramyl dipeptides (MDP) encapsulated within phospholipid vesicles (liposomes, MLV) leads to the activation of tumoricidal properties in mononuclear phagocytes and the eradication of established lymph node and pulmonary metastases. These studies were undertaken to elucidate the mechanism(s) by which MDP activates macrophages in vitro and in vivo, and to understand its potential for the therapy of disseminated cancer. The pharmacokinetics and metabolism of intravenously administered free (unencapsulated) and MLV-encapsulated (/sup 3/H)nor-MDP and its (/sup 3/H)-labeled lipophilic derivative, muramyl tripeptide phosphatidylethanolamine (MTP-PE) in mice demonstrated unique patterns of circulatory clearance, organ distribution, metabolism, and excretion. The in vitro activation of tumoricial properties in normal and gamma-interferon primed, noncytotoxic human blood monocytes by nor-MDP could be enhanced by its lipophilic derivatization (MTP-PE) or encapsulation within MLV. Studies using (/sup 3/H)nor-MDP and (/sup 3/H)MTP-PE revealed that the activation of monocytes by muramyl peptides could not be described as resulting from an interaction with MDP cell surface receptors nor from a nonspecific consequence of glycopeptide internalization but rather from a specific intracellular event. Efficient delivery of MDP to macrophages in vivo can be obtained via encapsulation in liposomes, MDP activated macrophages destroy tumor cells without apparent selectivity, and the systemic activation of macrophages by MDP has great potential for enhancing host defense against cancer.
- Research Organization:
- Maryland Univ., Baltimore (USA)
- OSTI ID:
- 7246214
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Inhibition of macrophage DNA synthesis by immunomodulators. II. Characterization of the suppression by muramyl dipeptide or lipopolysaccharide (/sup 3/H)thymidine incorporation into macrophages
Comparison of various assays to quantitate macrophage activation by biological response modifiers
Related Subjects
MACROPHAGES
CHEMICAL ACTIVATION
PEPTIDES
BIOCHEMISTRY
TUMOR CELLS
CELL KILLING
ENCAPSULATION
LIPOSOMES
METASTASES
MICE
PHOSPHOLIPIDS
RECEPTORS
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
CELL CONSTITUENTS
CHEMISTRY
CONNECTIVE TISSUE CELLS
ESTERS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANOIDS
PHAGOCYTES
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
550301* - Cytology- Tracer Techniques