Relationship of metabolism and immunostimulating activity of peptidoglycan monomer in mice after three different routes of administration

Abstract [ 14 C] Peptidoglycan monomer, GlcNAc-MurNAc- l -Ala- d -isoglutamine-meso-diaminopimelic acid (ωNH 2 )- d -Ala- d -Ala (PGM) was administered to mice by the intravenous (i.v.), subcutaneous (s.c.) or peroral (p.o.) routes. The data on distribution of radioactivity and excretion of radioactive products, as well as the data on immunostimulating effects are presented on the comparative basis for PGM administered by three different routes. When injected i.v. or s.c., the major part of applied radioactivity was found excreted in urine, partly as unchanged original compound and partly as the corresponding pentapeptide, l -ala- d -isoglutamine-meso-diaminopimelic acid ( ω NH 2 )- d - Ala - d - Ala . If administered p.o., the major part of the radioactivity was retained in the stomach and intestinal tract for several hours. The drop in radioactivity in these organs was followed by exhalation of 14 CO 2 thus indicating extensive degradation of the original molecule. PGM stimulates the humoral immune response to sheep red blood cells in mice if administered i.v. or s.c., but is completely inactive if administered p.o.. Thus, absence of immunostimulating activity following p.o. administration might be explained by extensive metabolic degradation of peptidoglycan monomer.