Regulation of developmental lymphangiogenesis by Syk(+) leukocytes.
Lymphatic vessels are essential for tissue homeostasis and immune surveillance and contribute to pathological conditions. Lymphatic endothelium differentiates from veins and forms an independent vascular tree with only few connections to the venous circulation. Failure of blood and lymphatic vessel separation results in hemorrhage and edema. VEGF-C and -D are strong inducers of lymphangiogenesis and have essential (VEGF-C) and modulatory (VEGF-D) roles during developmental lymphangiogenesis. We describe here a myeloid population that is defined by expression of the tyrosine kinase Syk, comprises largely M2-polarized mononuclear cells, and robustly expresses angiogenic factors, including VEGF-C/-D and chemokines. These cells stimulate lymphangiogenesis in vivo. Deletion of Syk causes increased chemotractant production, enhanced transmigration, and accumulation in the skin. Ensuing lymphatic hyperplasia and vessel dilation cause the formation of blood-lymphatic shunts. This mechanism does not involve circulating endothelial progenitor cells and demonstrates the potential of hematopoietic cells to control developmental lymphangiogenesis.
Department of Vascular Cell Biology, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Ruben
R
Böhmer
Brit
B
Neuhaus
Sebastian
S
Bühren
Dayong
D
Zhang
Martin
M
Stehling
Barbara
B
Böck
Friedemann
F
Kiefer
D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology; D018925:Chemokines / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D042601:Lymphatic Vessels / Q000196:embryology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D022423:Myeloid Cells / Q000502:physiology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000196:embryology; D000072377:Syk Kinase; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000502:physiology; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000502:physiology
D018925:Chemokines; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C467483:vascular endothelial growth factor C, mouse; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse