INTERLEUKIN-3 INDUCES ANTIMICROBIAL ACTIVITY AGAINST LEISHMANIA-AMAZONENSIS AND TRYPANOSOMA-CRUZI AND TUMORICIDAL ACTIVITY IN HUMAN PERIPHERAL BLOOD-DERIVED MACROPHAGES

被引:28
作者
HO, JL
REED, SG
SOBEL, J
ARRUDA, S
HE, SH
WICK, EA
GRABSTEIN, KH
机构
[1] SEATTLE BIOMED RES INST,SEATTLE,WA 98109
[2] IMMUNEX CORP,SEATTLE,WA 98101
关键词
D O I
10.1128/IAI.60.5.1984-1993.1992
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The ability of interleukin-3 (IL-3) to induce antimicrobial and tumoricidal activity was evaluated. Macrophages infected with two intracellular protozoa, Leishmania amazonensis or Trypanosoma cruzi, were treated with cytokines. IL-3 induced a dose-dependent enhancement of microbistasis against leishmanias, and the activity of IL-3 (100 ng/ml) was comparable to that of gamma interferon (IFN-gamma) (1,000 U/ml). In addition, IL-3 in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage CSF (M-CSF) or with IFN-gamma reduced infection and lowered the required dose. IL-3 similarly activated macrophages to inhibit intracellular replication of T. cruzi. Furthermore, IL-3 induced antibody-independent tumoricidal activity against melanoma cells that was dose dependent and comparable to that of lipopolysaccharide and GM-CSF. The mechanisms by which IL-3 induced antimicrobial activity may involve at least the augmentation of oxidative capacity. IL-3, at concentrations of 0.5 ng/ml or greater, led to a significantly increased oxidative burst which paralleled the inhibition of protozoan replication. The enhancement of oxidative capacity by IL-3 (5 ng/ml or higher) was comparable to that of IFN-gamma. The induction of tumoricidal activity was associated with the production of tumor necrosis factor alpha (TNF-alpha), which in this system may feed back to enhance the macrophage inhibition of leishmanias, as demonstrated by neutralization of IL-3 activation by anti-TNF-alpha antibody. Thus, peripheral blood macrophages remain responsive to IL-3, as demonstrated by enhanced antimicrobial and tumoricidal activity. IL-3 may have potential clinical applications because of these properties and its effect on myelopoiesis.
引用
收藏
页码:1984 / 1993
页数:10
相关论文
共 48 条
  • [1] BECKER S, 1987, J IMMUNOL, V139, P3703
  • [2] BERSANI L, 1986, IMMUNOLOGY, V59, P323
  • [3] CANNISTRA SA, 1988, BLOOD, V71, P672
  • [4] CLONING, SEQUENCE, AND EXPRESSION OF A HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR
    CANTRELL, MA
    ANDERSON, D
    CERRETTI, DP
    PRICE, V
    MCKEREGHAN, K
    TUSHINSKI, RJ
    MOCHIZUKI, DY
    LARSEN, A
    GRABSTEIN, K
    GILLIS, S
    COSMAN, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (18) : 6250 - 6254
  • [6] THE HUMAN HEMATOPOIETIC COLONY-STIMULATING FACTORS
    CLARK, SC
    KAMEN, R
    [J]. SCIENCE, 1987, 236 (4806) : 1229 - 1237
  • [7] DECKER T, 1987, J IMMUNOL, V138, P957
  • [8] DETITTO EH, 1986, J IMMUNOL, V137, P1342
  • [9] HUMAN IL-3 AND GM-CSF ACT SYNERGISTICALLY IN STIMULATING HEMATOPOIESIS IN PRIMATES
    DONAHUE, RE
    SEEHRA, J
    METZGER, M
    LEFEBVRE, D
    ROCK, B
    CARBONE, S
    NATHAN, DG
    GARNICK, M
    SEHGAL, PK
    LASTON, D
    LAVALLIE, E
    MCCOY, J
    SCHENDEL, PF
    NORTON, C
    TURNER, K
    YANG, YC
    CLARK, SC
    [J]. SCIENCE, 1988, 241 (4874) : 1820 - 1823
  • [10] ELLIOTT MJ, 1989, BLOOD, V74, P2349