title: Relationships between lymphangiogenesis and angiogenesis during inflammation in rat mesentery microvascular networks.
abstract: BACKGROUND
  Lymphatic and blood microvascular systems play a coordinated role in the regulation of interstitial fluid balance and immune cell trafficking during inflammation. The objective of this study was to characterize the temporal and spatial relationships between lymphatic and blood vessel growth in the adult rat mesentery following an inflammatory stimulus.
  
  
  RESULTS
  Mesenteric tissues were harvested from unstimulated adult male Wistar rats and at 3, 10, and 30 days post compound 48/80 stimulation. Tissues were immunolabeled for PECAM, LYVE-1, Prox1, podoplanin, CD11b, and class III β-tubulin. Vascular area, capillary blind end density, and vascular length density were quantified for each vessel system per time point. Blood vascular area increased compared to unstimulated tissues by day 10 and remained increased at day 30. Following the peak in blood capillary sprouting at day 3, blood vascular area and density increased at day 10. The number of blind-ended lymphatic vessels and lymphatic density did not significantly increase until day 10, and lymphatic vascular area was not increased compared to the unstimulated level until day 30. Lymphangiogenesis correlated with the upregulation of class III β-tubulin expression by endothelial cells along lymphatic blind-ended vessels and increased lymphatic/blood endothelial cell connections. In local tissue regions containing both blood and lymphatic vessels, the presence of lymphatics attenuated blood capillary sprouting.
  
  
  CONCLUSIONS
  Our work suggests that lymphangiogenesis lags angiogenesis during inflammation and motivates the need for future investigations aimed at understanding lymphatic/blood endothelial cell interactions. The results also indicate that lymphatic endothelial cells undergo phenotypic changes during lymphangiogenesis.
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Sweat
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stapor
authors.forename: Walter L
authors.initials: WL
authors.lastname: Murfee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D004729:Endothelium, Lymphatic / Q000473:pathology / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D042583:Lymphangiogenesis; D008208:Lymphatic System / Q000098:blood supply / Q000503:physiopathology; D042601:Lymphatic Vessels / Q000503:physiopathology; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000737:chemistry; D018613:Microscopy, Confocal; D055806:Microvessels / Q000737:chemistry / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D018398:Homeodomain Proteins; C509295:ITGAM protein, human; C119248:LYVE1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D003189:p-Methoxy-N-methylphenethylamine