Stimulation of cell proliferation in rabbits by MTP-PE, a lipophilic muramyl peptide

The in vivo effect of the lipophilic muramyl peptide MTP-PE on the proliferation of blood cells and various tissues of the rabbit was studied by means of 3H-thymidine. Animals were killed up to 120 h after one or two i.v. injections of MTP-PE (10 mg/kg). MTP-PE caused a drastic effect on white blood cells: (1) neutropenia and lymphocytopenia occurring within 5 h was followed by leukocytosis of neutrophils and their juvenile forms by 24 h and thereafter, (2) within 24 h the number of prelabelled, i.e. recently regenerated, mononuclear cells in the bone marrow and the vascular system of various tissues increased approximately threefold, and (3) within 48 h the concentration of proliferating monocytic cells (1-h pulse labelling) rose to maximum levels of up to 20-fold in the lumina of blood vessels, particularly in capillaries of many organs. The number of proliferating cells also increased in the adventitia of medium and small arteries with a maximum at 48 h, whereas this occurred only later in the media and hardly at all in the intima. Thus, these proliferating, apparently monocytic cells are blood derived, and migrate into the tissue within 24 h after MTP-PE administration. In addition, proliferation in the epithelium of the bile ducts and oesophagus was also stimulated with a maximum at 24 h after MTP-PE. In contrast, enhanced proliferation occurred more slowly and to a lesser extent in hepatocytes, hepatic interstitial cells, and renal epithelial cells, consistent with a regenerative process after an inflammatory or toxic event.