Technical Advance: The rat aorta contains resident mononuclear phagocytes with proliferative capacity and proangiogenic properties.
Angiogenesis in the aortic ring model is preceded by activation of the immune system and impaired by ablation of adventitial macrophages. Treatment of aortic cultures with M-CSF induced extensive periaortic outgrowth of CD45(+) CD68(+) mononuclear cells with ultrastructural features of macrophages and DCs. Periaortic lysis of collagen caused many CD45(+) CD68(+) cells to attach to the bottom of the culture dish. Lifting the collagen gels left behind patches of CD45(+) CD68(+) cells, which focally organized into branching cords. These cells also expressed CD14, CD169, F4/80, and α-SMA but not CD31, vWF, desmin, or CD163. DNA synthesis studies showed that M-CSF-stimulated cells were actively proliferating. Aortic patch cells showed phagocytic properties and responded to IL-4 and GM-CSF by expressing MHC II, differentiating into DCs, and forming multinucleated giant cells. They also stimulated angiogenesis and VEGF production in aortic ring cultures. This study demonstrates that the rat aorta contains a distinct subset of immature immunocytes capable of proliferating, differentiating into macrophages and DCs, and stimulating angiogenesis. Isolation of these cells in patches from M-CSF-stimulated aortic rings provides a reproducible system to study the biology and angiogenic role of the resident immune system of the aortic wall.
Zorzi
Penelope
P
VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA.
Aplin
Alfred C
AC
Smith
Kelly D
KD
Nicosia
Roberto F
RF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D002455:Cell Division; D017931:DNA Primers; D007124:Immunoenzyme Techniques; D017493:Leukocyte Common Antigens / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018613:Microscopy, Confocal / Q000379:methods; D018919:Neovascularization, Physiologic; D010586:Phagocytes / Q000166:cytology* / Q000187:drug effects; D010587:Phagocytosis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017931:DNA Primers; D017493:Leukocyte Common Antigens; D016173:Macrophage Colony-Stimulating Factor; C539355:CD68 protein, rat; D000097382:CD68 Molecule