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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5650-5659. Prepublished online as a Blood First Edition Paper on April 3, 2009; DOI 10.1182/blood-2008-09-176776. This Article Full Text (PDF) Supplemental Tables and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-09-176776v1 113/22/5650    most recent Alert me when this article is cited Alert me if a correction is posted 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 Kataru, R. P. Articles by Koh, G. Y. Search for Related Content PubMed PubMed Citation Articles by Kataru, R. P. Articles by Koh, G. Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 2, 2008 Accepted March 24, 2009 Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution Raghu P. Kataru, Keehoon Jung, Cholsoon Jang, Hanseul Yang, Reto A. Schwendener, Jung Eun Baik, Seung Hyun Han, Kari Alitalo, and Gou Young Koh* National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of Laboratory of Liposome Research, Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland Department of Oral Microbiology and Immunology, Dental Research Institute, School and BK21 Program of Dentistry, Seoul National University, Seoul, Korea, Republic of International Vaccine Institute, Seoul, Korea, Republic of The Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland * Corresponding author; email: gykoh{at}kaist.ac.kr. Using a bacterial pathogen-induced acute inflammation model in the skin, we defined the roles of local lymphatic vessels and draining lymph nodes (DLN) in antigen clearance and inflammation resolution. At the peak day of inflammation, robust expansion of lymphatic vessels and profound infiltration of CD11b+/Gr-1+ macrophages into the inflamed skin and DLN were observed. Moreover, lymph flow and inflammatory cell migration from the inflamed skin and DLN were enhanced. Concomitantly, the expression of lymphangiogenic growth factors such as vascular endothelial growth factor (VEGF)-C, -D and -A were significantly up-regulated in the inflamed skin, DLN, and particularly in enriched CD11b+ macrophages from the DLN. Depletion of macrophages, or blockade of VEGF-C/D or VEGF-A, largely attenuated these phenomena, and produced notably delayed antigen clearance and inflammation resolution. Conversely, keratin 14 (K14)-VEGF-C transgenic mice, which have dense and enlarged lymphatic vessels in the skin dermis, exhibited accelerated migration of inflammatory cells from the inflamed skin to the DLN and faster antigen clearance and inflammation resolution. Taken together, these results indicated that VEGF-C, -D and -A derived from the CD11b+/Gr-1+ macrophages and local inflamed tissues play a critical role in promoting antigen clearance and inflammation resolution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. E. Kim, Y.-J. Koh, B.-H. Jeon, C. Jang, J. Han, R. P. Kataru, R. A. Schwendener, J.-M. Kim, and G. Y. Koh Role of CD11b+ Macrophages in Intraperitoneal Lipopolysaccharide-Induced Aberrant Lymphangiogenesis and Lymphatic Function in the Diaphragm Am. J. Pathol., October 1, 2009; 175(4): 1733 - 1745. [Abstract] [Full Text] [PDF]

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