CEACAM1+ myeloid cells control angiogenesis in inflammation.
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.
Horst
Andrea K
AK
Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. ahorst@uke.uni-hamburg.de
Bickert
Thomas
T
Brewig
Nancy
N
Ludewig
Peter
P
van Rooijen
Nico
N
Schumacher
Udo
U
Beauchemin
Nicole
N
Ito
Wulf D
WD
Fleischer
Bernhard
B
Wagener
Christoph
C
Ritter
Uwe
U
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen; D004338:Drug Combinations; D004487:Edema / Q000209:etiology / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis; D007111:Immunity, Cellular; D020007:Implants, Experimental; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007797:Laminin; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D042601:Lymphatic Vessels / Q000378:metabolism; D008264:Macrophages / Q000469:parasitology / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D011509:Proteoglycans; D011828:Radiation Chimera; D018417:Th1 Cells / Q000276:immunology
D000913:Antibodies, Protozoan; D039481:CD11b Antigen; D002272:Carcinoembryonic Antigen; D003094:Collagen; D004338:Drug Combinations; D006023:Glycoproteins; D007371:Interferon-gamma; D007797:Laminin; D026901:Membrane Transport Proteins; D011509:Proteoglycans; C486183:Ceacam1 protein, mouse; C492273:LYVE1 protein, mouse; C059485:matrigel