This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Poste, G. Articles by Fidler, I. J. Search for Related Content PubMed PubMed Citation Articles by Poste, G. Articles by Fidler, I. J.

Activation of Tumoricidal Properties in Mouse Macrophages by Lymphokines Encapsulated in Liposomes¹

Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, New York 14263 [G. P., R. K.], and Cancer Biology Program, National Cancer Institute Frederick Cancer Research Center, Frederick, Maryland 21701 [W. F., I. J. F.]

Cell-free culture supernatants rich in macrophage-activating factor (MAF) activity obtained from mitogen-stimulated F344 rat lymphocytes have been encapsulated within liposomes of differing size and lipid composition and their ability to render normal mouse macrophages cytotoxic for tumor cells in vitro has been compared with that of unencapsulated (free) MAF added to the extracellular medium. Normal macrophages from C57BL/6, C3H/Hen, and C57BL/6 x C3H F₁ mice treated with liposome-encapsulated MAF exhibited significant in vitro cytotoxicity against syngeneic and allogeneic tumor cells but did not kill nontumorigenic normal cells. Dose-response measurements revealed that liposome-encapsulated MAF was able to render macrophages tumoricidal at concentrations of at least 20,000 times lower than free MAF. Liposomes containing MAF were able to activate macrophages in the presence of p-nitrophenyl-2-O--L-fucopyranosyl-ß-D-galactopyranoside, a potent inhibitor of free MAF, indicating that encapsulated MAF was protected within liposomes and that liposome-mediated activation was not caused by small amounts of MAF released into the culture medium from "leaky" liposomes. Liposome-encapsulated MAF was also able to activate macrophages which were refractory to activation by free MAF following either removal of presumably surface receptors for MAF by pronase and/or -L-fucosidase or occupation of the MAF receptor on macrophages by fucose-binding plant lectins (Ulex europaeus I and Lotus tetragonolobus agglutinins). Also, populations of nontumoricidal inflammatory tissue macrophages, which were inherently unresponsive to free MAF, could be rendered tumoricidal in vitro by incubation with liposome-encapsulated MAF. Collectively, the data suggest that MAF can render macrophages tumoricidal by acting on intracellular sites.

¹ Research sponsored by USPHS Research Grants CA 13393 and CA18260; NIH Core Support Grant CA17609 to Roswell Park Memorial Institute, Cancer Cell Center; and National Cancer Institute Contract NO1-CO-75380 with Litton Bionetics, Inc.

² To whom requests for reprints should be addressed.

Received 9/22/78. Accepted 12/ 1/78.

This article has been cited by other articles:

				W. Koff, I. Fidler, S. Showalter, M. Chakrabarty, B Hampar, L. Ceccorulli, and E. Kleinerman Human monocytes activated by immunomodulators in liposomes lyse herpesvirus-infected but not normal cells Science, June 1, 1984; 224(4652): 1007 - 1009. [Abstract] [PDF]

				I. Fidler Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines Science, June 27, 1980; 208(4451): 1469 - 1471. [Abstract] [PDF]