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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6726-6736.
Prepublished online as a Blood First Edition Paper on March 9, 2009; DOI 10.1182/blood-2008-10-184556.


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VASCULAR BIOLOGY

CEACAM1+ myeloid cells control angiogenesis in inflammation

Andrea K. Horst1,*, Thomas Bickert1,2,*, Nancy Brewig2, Peter Ludewig1, Nico van Rooijen3, Udo Schumacher4, Nicole Beauchemin5, Wulf D. Ito6, Bernhard Fleischer2, Christoph Wagener1, and Uwe Ritter2,7

1 Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2 Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; 3 Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit Medical Center (VUMC), Amsterdam, The Netherlands; 4 Department of Anatomy II: Experimental Morphology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5 McGill Cancer Centre, McGill University, Montreal, QC; 6 Department of Internal Medicine II, University of Ulm, Ulm, Germany; and 7 Department of Immunology, University of Regensburg, Regensburg, Germany

Local inflammation during cutaneous leishmaniasis is accompanied by accumulation of CD11b+ cells at the site of the infection. A functional role for these monocytic cells in local angiogenesis in leishmaniasis has not been described so far. Here, we show that CD11b+ cells express high levels of the myeloid differentiation antigen carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). In experimental cutaneous leishmaniasis in C57BL/6 wild-type (B6.WT) and B6.Ceacam1–/– mice, we found that only B6.Ceacam1–/– mice develop edemas and exhibit impairment of both hemangiogenesis and lymphangiogenesis. Because CEACAM1 expression correlates with functional angiogenesis, we further analyzed the role of the CD11b+ population. In B6.Ceacam1–/– mice, we found systemic reduction of Ly-6Chigh/CD11bhigh monocyte precursors. To investigate whether CEACAM1+ myeloid cells are causally related to efficient angiogenesis, we used reverse bone marrow transplants (BMTs) to restore CEACAM1+ or CEACAM1 bone marrow in B6.Ceacam1–/– or B6.WT recipients, respectively. We found that angiogenesis was restored by CEACAM1+ BMT only. In addition, we observed reduced morphogenic potential of inflammatory cells in Matrigel implants in CEACAM1 backgrounds or after systemic depletion of CD11bhigh macrophages. Taken together, we show for the first time that CEACAM1+ myeloid cells are crucial for angiogenesis in inflammation.


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Related Article in Blood Online:

Myeloid cell–induced angiogenesis: a sticky business
Anna M. Randi and Benedetta Bussolati
Blood 2009 113: 6508-6510. [Full Text] [PDF]



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A. M. Randi and B. Bussolati
Myeloid cell-induced angiogenesis: a sticky business
Blood, June 25, 2009; 113(26): 6508 - 6510.
[Full Text] [PDF]



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