RESUMO
BACKGROUND: The origin of cardiac lymphatics from venous endothelial cells or from scattered lymphangioblasts has been discussed in the literature. We aimed to establish the stage when lymphatic vessels appear in the developing mouse heart, the location of the first lymphatics, and to define cellular phenotypes of growing lymphatics. RESULTS: We found that scattered Lyve-1-positive cells located in the subepicardial area of developing heart expressed CD45, CD68, F4/80, or CD11b but not CD31. Prox-1(+)/Lyve-1(+) cellular cords or vessels were found to invade 12.5-13.5-dpc hearts via two routes: from the venous pole, i.e., dorsal atrioventricular sulcus, or on the dorsal atrial surface from mediastinum and from the arterial pole, i.e., along the great arteries. The Prox-1(+)/Lyve-1(+) vessels were located among the Prox-1(+)/Lyve-1(-) cords and among the scattered Prox-1(-)/Lyve-1(+) cells. The Prox-1(+)/Lyve-1(-) cellular cords/tubules dominate initially at the arterial pole whereas Lyve-1(+)/Prox-1(-) cellular cords/tubules dominate initially on the venous pole, i.e., dorsal atrioventricular sulcus. The Lyve-1(+)/CD45(+), Lyve-1(+)/CD11b(+), Lyve-1(+)/F4/80(+) and Lyve-1(+)/CD68(+) cells were subsequently found to be co-opted to the wall of the developing lymphatic vessels while gaining Flk-1. CONCLUSIONS: Lymphatic primordia exhibit different cellular phenotypes and different spatiotemporal pattern on the venous pole as compared with the arterial pole of the heart.
Assuntos
Padronização Corporal , Coração/embriologia , Linfangiogênese , Vasos Linfáticos/citologia , Vasos Linfáticos/embriologia , Animais , Padronização Corporal/genética , Padronização Corporal/fisiologia , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Glicoproteínas/genética , Glicoproteínas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Linfangiogênese/genética , Linfangiogênese/fisiologia , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Modelos Biológicos , Miocárdio/citologia , Miocárdio/imunologia , Organogênese/genética , Organogênese/fisiologia , Fenótipo , Fatores de Tempo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Natural anti-chondrocyte cytotoxicity of normal rat splenocytes, peritoneal cells and thymocytes was tested by means of 51Cr-release assay. Chondrocytes derived from epiphyseal, costal, nasal, and auricular cartilages were used as target cells. In some experiments, erythroleukaemic K-562 cells, known as typical natural killer cell targets, were also used. All types of chondrocytes were lysed equally well by splenocytes. Peritoneal cells exerted a low cytotoxic effect, whilst very low, almost negligible, cytotoxicity was noted with thymocytes. Negative selection with antibodies and complement showed that spleen-derived anti-chondrocyte effector cells are endowed with surface ganglioside asialo-GM1. A similar result was obtained in parallel experiments with K-562 cells. Moreover, 'cold' target experiments demonstrated that the release of 51Cr from the labelled chondrocytes could be inhibited by addition of unlabelled chondrocytes and K-562 cells.
