Expression of Tie-2 by human monocytes and their responses to angiopoietin-2

被引:242
作者
Murdoch, Craig [1 ]
Tazzyman, Simon [1 ]
Webster, Steve [1 ]
Lewis, Claire E. [1 ]
机构
[1] Univ Sheffield, Sch Med, Sir Henry Wellcome Labs Med Res, Div Genom Med,Acad Unit Pathol,Tumor Targeting Gr, Sheffield S10 2RX, S Yorkshire, England
关键词
D O I
10.4049/jimmunol.178.11.7405
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Angiopoietins 1 and 2 bind to Tie-2 expressed on endothelial cells and regulate vessel stabilization and angiogenesis. Tie-2(+) monocytes have been shown to be recruited to experimental tumors where they promote tumor angiogenesis. In this study, we show that 20% of CD14(+) human blood monocytes express Tie-2, and that these cells coexpress CD16 (Fc gamma RIII) and are predominantly CD34 negative. Ang-2 is up-regulated by endothelial cells in malignant tumors and inflamed tissues, so our finding that Ang-2 is a chemoattractant for human Tie-2(+) monocytes and macrophages, suggests that it may help to recruit and regulate their distribution in such tissues. Ang-2 was also found to markedly inhibit release of the important proinflammatory cytokine, TNF-alpha, by monocytes in vitro. Following extravasation of monocytes, and their differentiation into macrophages, many accumulate in the hypoxic areas of inflamed and malignant tissues. Ang-2 is known to be up-regulated by hypoxia and we show that monocytes and macrophages up-regulate Tie-2 when exposed to hypoxia. Furthermore, hypoxia augmented the inhibitory effect of Ang-2 on the release of the anti-angiogenic cytokine, IL-12 by monocytes. In sum, our data indicate that Ang-2 may recruit Tie-2(+) monocytes to tumors and sites of inflammation, modulate their release of important cytokines and stimulate them to express a proangiogenic phenotype.
引用
收藏
页码:7405 / 7411
页数:7
相关论文
共 46 条
[1]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[2]   Activation of Tie2 by angiopoietin-1 and angiopoietin-2 results in their release and receptor internalization [J].
Bogdanovic, Elena ;
Nguyen, Vicky P. K. H. ;
Dumont, Daniel J. .
JOURNAL OF CELL SCIENCE, 2006, 119 (17) :3551-3560
[3]   Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by macrophages [J].
Bosco, MC ;
Puppo, M ;
Pastorino, S ;
Mi, ZH ;
Melillo, G ;
Massazza, S ;
Rapisarda, A ;
Varesio, L .
JOURNAL OF IMMUNOLOGY, 2004, 172 (03) :1681-1690
[4]   Dual functional roles of Tie-2/angiopoietin in TNF-α-mediated angiogenesis [J].
Chen, JX ;
Chen, Y ;
DeBusk, L ;
Lin, WY ;
Lin, PC .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (01) :H187-H195
[5]   Interleukin-12 in anti-tumor immunity and immunotherapy [J].
Colombo, MP ;
Trinchieri, G .
CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (02) :155-168
[6]   Isolation of Angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning [J].
Davis, S ;
Aldrich, TH ;
Jones, PF ;
Acheson, A ;
Compton, DL ;
Jain, V ;
Ryan, TE ;
Bruno, J ;
Radziejewski, C ;
Maisonpierre, PC ;
Yancopoulos, GD .
CELL, 1996, 87 (07) :1161-1169
[7]   Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells [J].
De Palma, M ;
Venneri, MA ;
Roca, C ;
Naldini, L .
NATURE MEDICINE, 2003, 9 (06) :789-795
[8]   Tie2 identifies a hematopoietic monocytes required for tumor lineage of proangiogenic vessel formation and a mesenchymal population of pericyte progenitors [J].
De Palma, M ;
Venneri, MA ;
Galli, R ;
Sergi, LS ;
Politi, LS ;
Sampaolesi, M ;
Naldini, L .
CANCER CELL, 2005, 8 (03) :211-226
[9]   A 48-WELL MICRO CHEMOTAXIS ASSEMBLY FOR RAPID AND ACCURATE MEASUREMENT OF LEUKOCYTE MIGRATION [J].
FALK, W ;
GOODWIN, RH ;
LEONARD, EJ .
JOURNAL OF IMMUNOLOGICAL METHODS, 1980, 33 (03) :239-247
[10]   Expression and function of the angiopoietin receptor Tie-2 in human eosinophils [J].
Feistritzer, C ;
Mosheimer, BA ;
Sturn, DH ;
Bijuklic, K ;
Patsch, JR ;
Wiedermann, CJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 114 (05) :1077-1084