CEACAM1+ myeloid cells control angiogenesis in inflammation

Abstract

AbstractLocal 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.