Prolactin regulates antitumor immune response through induction of tumoricidal macrophages and release of IL-12

被引:43
作者
Majumder, B [1 ]
Biswas, R [1 ]
Chattopadhyay, U [1 ]
机构
[1] Chittaranjan Natl Canc Inst, Dept Immunoregulat & Immunodiag, Kolkata 700026, India
关键词
prolactin; interferon-γ interleukin-12; inflammatory macrophage; tumor-associated macrophage;
D O I
10.1002/ijc.1624
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL-Rs in a cells. Here, we show that PRL, though it failed to activate mouse peritoneal resident macrophages (RMs), acted as a second signal and activated mouse peritoneal inflammatory macrophages (EMs) to a tumoricidal state. The cytotoxicity of mouse tumor-associated macrophages (TAMs) isolated at day 1 of tumor (Ehrlich ascites carcinoma, EAC) growth was enhanced by PRL. However, with progression of tumor growth, TAMs became nonresponsive to the hormone. PRL-induced killing of P815 target cells by EMs and TAMs was independent of TNF but correlated with the hormone-induced augmentation of NO2- and O-2 release in these macrophages. Administration of PRL in vivo inhibited EAC growth and augmented NO2- release by TAMs. PRL synergized with the TH1 cytokine IFN-gamma a known activator of macrophages, in inducing tumor killing and release of NO2- from EMs and TAMs. The hormone might activate macrophages at least partially, through the release of IFN-gamma as anti-IFN-gamma blocked IFN-gamma- as well as PRL-induced cytotoxicity in EMs. The TH2 cytokine IL-4 suppressed PRL-induced activation of macrophages. PRL induced release of IL-12 from EMs also, which suggested that the hormone might drive the TH1 response through IL-12. Our observations further suggest that PRL alone and in synergy with IFN-gamma, released through induction of IL-12, may generate tumoricidal macrophages and thus regulate the antitumor immune response of tumor hosts. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:493 / 500
页数:8
相关论文
共 66 条
[1]   Do macrophages kill through apoptosis? [J].
Aliprantis, AO ;
DiezRoux, G ;
Mulder, LCF ;
Zychlinsky, A ;
Lang, RA .
IMMUNOLOGY TODAY, 1996, 17 (12) :573-576
[3]   Tumor-associated transforming growth factor-β and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients [J].
Bellone, G ;
Turletti, A ;
Artusio, E ;
Mareschi, K ;
Carbone, A ;
Tibaudi, D ;
Robecchi, A ;
Emanuelli, G ;
Rodeck, U .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (02) :537-547
[4]   SUPPRESSION OF MACROPHAGE ACTIVATION AND LYMPHOCYTE-T FUNCTION IN HYPOPROLACTINEMIC MICE [J].
BERNTON, EW ;
MELTZER, MS ;
HOLADAY, JW .
SCIENCE, 1988, 239 (4838) :401-404
[5]   ALTERED PROLACTIN RESPONSE OF THE LYMPHOCYTES OF TUMOR-BEARING MICE [J].
BISWAS, R ;
CHATTOPADHYAY, U .
INTERNATIONAL JOURNAL OF CANCER, 1992, 50 (01) :93-98
[6]  
Bouchard B, 1999, J IMMUNOL, V163, P576
[7]   HEMATOPOIETIN SUBFAMILY CLASSIFICATION BASED ON SIZE, GENE ORGANIZATION AND SEQUENCE HOMOLOGY [J].
BOULAY, JL ;
PAUL, WE .
CURRENT BIOLOGY, 1993, 3 (09) :573-581
[8]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[9]  
CASSATELLA MA, 1990, J BIOL CHEM, V265, P20241
[10]  
CESSARIO TC, 1994, P SOC EXP BIOL MED, V205, P89