CEACAM1+ myeloid cells control angiogenesis in inflammation

Blood. 2009 Jun 25;113(26):6726-36. doi: 10.1182/blood-2008-10-184556. Epub 2009 Mar 9.

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-6C(high)/CD11b(high) 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 CD11b(high) macrophages. Taken together, we show for the first time that CEACAM1(+) myeloid cells are crucial for angiogenesis in inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Bone Marrow Transplantation
  • CD11b Antigen / analysis
  • Carcinoembryonic Antigen / analysis*
  • Carcinoembryonic Antigen / biosynthesis
  • Carcinoembryonic Antigen / genetics
  • Collagen
  • Drug Combinations
  • Edema / etiology
  • Edema / pathology
  • Glycoproteins / biosynthesis
  • Immunity, Cellular
  • Implants, Experimental
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / physiopathology*
  • Interferon-gamma / biosynthesis
  • Laminin
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / complications
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / pathology
  • Leishmaniasis, Cutaneous / physiopathology*
  • Lymphatic Vessels / metabolism
  • Macrophages / parasitology
  • Macrophages / physiology
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / chemistry
  • Myeloid Cells / classification
  • Myeloid Cells / physiology*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology*
  • Proteoglycans
  • Radiation Chimera
  • Th1 Cells / immunology

Substances

  • Antibodies, Protozoan
  • CD11b Antigen
  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Drug Combinations
  • Glycoproteins
  • Laminin
  • Membrane Transport Proteins
  • Proteoglycans
  • Xlkd1 protein, mouse
  • matrigel
  • Interferon-gamma
  • Collagen