Activation of rat alveolar macrophages and protection against i.v. injected tumor cells by intratracheal administration of trehalose dimycolate

Abstract

Intratracheal (i.t.) administration of trehalose dimycolate (TDM) in saline as liposomes induces a transient inflammatory effect. Limited granulomas appeared in some peribronchial areas but most subsided after a few weeks. The alveolar macrophages were activated as judged by their cytostatic activity against the syngeneic P77 fibrohistiocytoma 3 days after administration of 0.2 mg TDM. The NK activity of the lymphocytes of the lung microcirculation did not increase and diminished slightly between 1 and 3 days after TDM administration, thus suggesting that macrophages might be the main effector cells responding to TDM. Repeated i.t. TDM administration protected rats against the development of colonies in the lung after i.v. injection of 5 X 10(5) P77 cells. The survival of the rats was significantly increased. Thus, in this system, a relationship exists between activation of alveolar macrophages and protection against colonies arising from i.v. injected tumor cells.

Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions

“…Similar data have been reported previously by Lepoivre et al in trehalose diester (TDM)-elicited macrophages [26]. Such a decrease seems to be characteristic of activated macrophages which exhibit a strong cytostatic capacity against syngeneic tumors; for example those elicited by TDM or C.parvum [9,28,29].…”

“…In contrast, without LPS (10ng/ml) treatment of the macrophages, the mast0cytoma exhibited some residual growth, indicating that CW-and NWSM-treated macrophages are not fully activated but need a second signal to express their cytostatic activity fully. These results are in accordance with those found using other activating agents [18,26,29].…”

“…The cytostatic effect of macrophages on P815 mastocytoma cells was quantified as previously described [18,29]. Briefly, after adherence the macrophage monolayers (1 × 10 6 cells/ ml) were washed twice with PBS to eliminate nonadherent cells, and incubated with lipopolysaccharide (LPS) (10 ng/ ml) for 4 h. A suspension of P815 (0.3 x 10 6 cells/ml) and 1.2 ~tM SH-TdR (CEA, France sp.…”

Role of Trehalose Dimycolate in Recruitment of Cells and Modulation of Production of Cytokines and NO in Tuberculosis

“…TDM is a potent immunomodulator that increases nonspecific resistance to infectious agents and limits tumor growth (12,16,20). Direct or indirect attraction of macrophages by TDM to the site of inoculation may be one component of its mechanism of action.…”

“…Four decades of research on TDM have uncovered a number of biological activities involved in the pathogenesis of mycobacterial diseases, including high toxicity to mice (3) and immunomodulation (12). Several other effects of TDM in addition to its toxicity (28), such as the development of a granulomatous reaction in mouse lungs after intravenous administration (21), adjuvant and immunostimulatory properties (10), and capacity to enhance nonspecific resistance to tumors (12,16) and to bacterial infections (20,22) in mice, suggest the participation of TDM in the host-parasite relationship at different levels. Indirect evidence has also been provided that TDM might be responsible for inhibiting fusion between adjacent membranes in vivo (29), suggesting a role in inhibition of phagosome-lysosomal fusion.…”