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. Methods and 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 b-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 b-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.

Printing cancer cells into intact microvascular networks: a model for investigating cancer cell dynamics during angiogenesis

“…10–12 Lymphatic identity based on these features is supported by our previous co-labeling of lymphatic vessels with lectin or PECAM and typical lymphatic markers: LYVE-1, 8,10–12 Prox1, 10–12 and podoplanin. 10–12 Arterioles, venules, and capillaries were identified by position in the network, vessel morphology, and labeling intensity as previously described. 8 Following printing, MDA-MB-231 cells attached to the tissue substrate and maintained their initially deposited positions.…”

Lymphangiogenesis in rat asthma model

“…Our results demonstrate an increase in bronchial blood vessels at the time when we observed an increase in lymphatic vessel numbers. Perhaps relevant to this observation are results of Sweat and colleagues who showed that in the mesentery, angiogenesis always preceded lymphangiogenesis (28, 48). Treatment with VEGF-C, the most prominent lymphangiogenic factor, led first to angiogenesis followed by subsequent lymphangiogenesis.…”

Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks

“…The six lymphatic networks ranged in network area (12-129 mm 2 ), maximum branch order (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and total number of segments (31-219) (Figs. 2; 3A-C).…”