MACROPHAGE DEPLETION IN THE RAT AFTER INTRAPERITONEAL ADMINISTRATION OF LIPOSOME-ENCAPSULATED CLODRONATE - DEPLETION KINETICS AND ACCELERATED REPOPULATION OF PERITONEAL AND OMENTAL MACROPHAGES BY ADMINISTRATION OF FREUNDS-ADJUVANT

The purpose of this study was to develop a method for the depletion of macrophages from the peritoneal cavity and the omentum of the rat. Ra ts received two intraperitoneal injections (at days 0 and 3) with lipo some-encapsulated clodronate (dichloromethylene bisphosphonate: Cl(2)M BP-liposomes). This treatment resulted in complete elimination of matu re tissue macrophages (ED2-positive macrophages) from the peritoneal c avity and the omentum within 2 days. The elimination included the stro ngly ED2-positive spindle-shaped cells of the omental membrane. Repopu lation of the omental ED2-positive macrophages was not seen within the next 23 days. Whereas ED2-positive macrophages were completely deplet ed, few ED1-positive cells remained and repopulation of ED1-positive c ells was faster. The treatment further depleted macrophages from the s pleen, especially from the red pulp, parathymic lymph nodes and liver. Freund's incomplete adjuvant administered one day after the last inje ction of Cl(2)MBP-liposomes considerably accelerated repopulation in t he omentum. The protocol described might be used to investigate the co ntribution of mature tissue macrophages to the induction of immune res ponses, drug metabolism and the elimination of intestinal tumours.