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Blood, 1 January 2006, Vol. 107, No. 1, pp. 317-327. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-04-1458. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1458v1 107/1/317    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zijlstra, A. Articles by Deryugina, E. I. Search for Related Content PubMed PubMed Citation Articles by Zijlstra, A. Articles by Deryugina, E. I. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells Andries Zijlstra, Marco Seandel, Tatyana A. Kupriyanova, Juneth J. Partridge, Mark A. Madsen, Elizabeth A. Hahn-Dantona, James P. Quigley, and Elena I. Deryugina From the Department of Cell Biology, The Scripps Research Institute, La Jolla, CA; the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; and the Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, MD. A quantitative in vivo angiogenesis model employing collagen onplants placed on the chick embryo chorioallantoic membrane (CAM) has been used in this study to assess the spatial and temporal associations between neutrophil-like inflammatory cells, namely chicken heterophils, and the development of new blood vessels. Previously we have demonstrated that monocytes/macrophages infiltrating the onplants were associated with extracellular matrix remodeling and angiogenesis, in particular by delivering MMP-13 collagenase. By introducing chicken gelatinase B (chMMP-9) as a specific marker for heterophils, we now show that the onset and extent of angiogenesis induced by purified growth factors or by human HT-1080 fibrosarcoma cells correlated with the initial influx of chMMP-9–positive heterophils. This early heterophil arrival was followed by the infiltration of monocytes/macrophages and appeared to sustain further blood vessel formation. The disruption of inflammatory cell influx by 2 mechanistically distinct anti-inflammatory drugs, cortisone and ibuprofen, significantly inhibited angiogenesis, indicating a functional involvement of these inflammatory cells in new blood vessel development. A direct addition of isolated heterophils or purified chMMP-9 into the HT-1080 onplants engrafted into cortisone- or ibuprofen-treated embryos reversed the antiangiogenic effects of the drugs. The exogenously added heterophils induced in vivo a further infiltration of endogenous heterophils and monocytes and dramatically rescued the impaired angiogenesis, highlighting the importance of early inflammatory leukocytes in tumor-induced angiogenesis. Moreover, purified heterophils incorporated into onplants lacking growth factors or tumor cells induced angiogenesis in nontreated embryos, further indicating a direct proangiogenic role for neutrophil-like leukocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. C. Ardi, T. A. Kupriyanova, E. I. Deryugina, and J. P. Quigley Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis PNAS, December 18, 2007; 104(51): 20262 - 20267. [Abstract] [Full Text] [PDF] J. J. Partridge, M. A. Madsen, V. C. Ardi, T. Papagiannakopoulos, T. A. Kupriyanova, J. P. Quigley, and E. I. Deryugina Functional Analysis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Differentially Expressed by Variants of Human HT-1080 Fibrosarcoma Exhibiting High and Low Levels of Intravasation and Metastasis J. Biol. Chem., December 7, 2007; 282(49): 35964 - 35977. [Abstract] [Full Text] [PDF] T. Nitto, K. D. Dyer, M. Czapiga, and H. F. Rosenberg Evolution and Function of Leukocyte RNase A Ribonucleases of the Avian Species, Gallus gallus J. Biol. Chem., September 1, 2006; 281(35): 25622 - 25634. [Abstract] [Full Text] [PDF]

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