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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.
Submitted October 21, 2008
Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany * Corresponding author; email: ahorst{at}uke.uni-hamburg.de.
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 oedemas and exhibit impairment of both hem- and lymphangiogenesis. Since 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 (BMT) 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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