CEACAM1+ myeloid cells control angiogenesis in inflammation

AK Horst, T Bickert, N Brewig, P Ludewig… - Blood, The Journal …, 2009 - ashpublications.org
AK Horst, T Bickert, N Brewig, P Ludewig, N van Rooijen, U Schumacher, N Beauchemin
Blood, The Journal of the American Society of Hematology, 2009ashpublications.org
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 …
Abstract
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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