Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes

George Poste, R. Kirsh, W. E. Fogler, I. J. Fidler

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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 form C57BL/6, C3H/Hen, and C57BL/6 x C3H F1, mice treated with liposome-encapculated 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-α-L-fucopyranosyl-β-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 α-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 suggests that MAF can render macrophages tumoricidal by acting on intracellular sites.

Original languageEnglish (US)
Pages (from-to)881-892
Number of pages12
JournalCancer Research
Volume39
Issue number3
StatePublished - 1979
Externally publishedYes

Fingerprint

Macrophage-Activating Factors
Lymphokines
Liposomes
Macrophages
alpha-L-Fucosidase
Plant Lectins
Ulex

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. / Poste, George; Kirsh, R.; Fogler, W. E.; Fidler, I. J.

In: Cancer Research, Vol. 39, No. 3, 1979, p. 881-892.

Research output: Contribution to journalArticle

Poste, George ; Kirsh, R. ; Fogler, W. E. ; Fidler, I. J. / Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. In: Cancer Research. 1979 ; Vol. 39, No. 3. pp. 881-892.
@article{af7d67751eb3489db8974b72f2bab427,
title = "Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes",
abstract = "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 form C57BL/6, C3H/Hen, and C57BL/6 x C3H F1, mice treated with liposome-encapculated 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-α-L-fucopyranosyl-β-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 α-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 suggests that MAF can render macrophages tumoricidal by acting on intracellular sites.",
author = "George Poste and R. Kirsh and Fogler, {W. E.} and Fidler, {I. J.}",
year = "1979",
language = "English (US)",
volume = "39",
pages = "881--892",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes

AU - Poste, George

AU - Kirsh, R.

AU - Fogler, W. E.

AU - Fidler, I. J.

PY - 1979

Y1 - 1979

N2 - 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 form C57BL/6, C3H/Hen, and C57BL/6 x C3H F1, mice treated with liposome-encapculated 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-α-L-fucopyranosyl-β-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 α-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 suggests that MAF can render macrophages tumoricidal by acting on intracellular sites.

AB - 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 form C57BL/6, C3H/Hen, and C57BL/6 x C3H F1, mice treated with liposome-encapculated 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-α-L-fucopyranosyl-β-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 α-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 suggests that MAF can render macrophages tumoricidal by acting on intracellular sites.

UR - http://www.scopus.com/inward/record.url?scp=0018768663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018768663&partnerID=8YFLogxK

M3 - Article

VL - 39

SP - 881

EP - 892

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 3

ER -