THE ACTIVATION OF TUMORICIDAL PROPERTIES IN MACROPHAGES OF ENDOTOXIN RESPONDER AND NONRESPONDER MICE BY LIPOSOME-ENCAPSULATED IMMUNOMODULATORS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 33  (3) , 165-174
Abstract
The purpose of these studies was to determine whether various immunomodulators such as lipopolysaccharide (LPS), lymphokines with macrophage activation factor (MAF) or muramyl dipeptide (MDP) could activate the tumoricidal properties in LPS-responsive C3H/HeN and LPS-unresponsive C3H/HeJ mice. In all studies the interaction of the different immunomodulators was examined in a free form or encapsulated within liposomes (multilamellar vesicles) with alveolar macrophages (AM) and/or peritoneal exudate macrophages (PEM). In vivo infection with viable Mycobacterium bovis, strain BCG, induced the development of highly activated macrophages from C3H/HeN mice, yet only marginally activated macrophages from C3H/HeJ mice. In vitro incubation with MAF or LPS rendered AM and PEM from C3H/HeN, but not C3H/HeJ, mice tumoricidal. The failure of C3H/HeJ macrophages to respond to LPS stimulation was due to an intracellular defect. C3H/HeJ macrophages bound fluorescein-comnjugated LPS to the same extent as that found for C3H/HeN macrophages. LPS encapsulated in liposomes activated C3H/HeN but not C3H/HeJ AM and/or PEM. Macrophages from both strains could be rendered highly tumoricidal following interaction with free MDP or following endocytosis of liposomes containing MDP or MAF. The inability of C3H/HeJ macrophages to respond to LPS stimulation is apparently specific and the activation of macrophages by different immunomodulators could occur by different pathways.