To fulfill the roles the lymphatic system plays in body fluid regulation, macromolecular homeostasis, lipid absorption, immune function, it must transport lymph from the interstitium, along the lymphatic network, through the nodes, into the great veins of the neck. Lymphatic muscle utilizes a unique combination of tonic and phasic contractions and muscle contractile proteins to generate and control lymph flow/transport. Contraction of lymphatic muscle is driven and regulated by both physical and ionic events. Stretch of the lymphatic wall is the most well documented physical stimulator of lymphatic function. Lymphatic muscle ionic events drive the electrical activity and intracellular calcium to modulate contraction. However, the ionic mechanisms regulating lymphatic muscle contraction and how stretch activates them are relatively unknown. To gain a better understanding of the regulation of lymphatic function, we propose to investigate the ionic mechanisms of lymphatic muscle contraction and how they are affected by stretch in isolated rat mesenteric lymphatics. Dysfunctional lymphatics result in a wide range of clinical problems. This project will substantially advance our understanding of lymphatic biology and provide the basis for the eventual development of therapeutic strategies to diagnose and treat lymphatic contractile dysfunction.
To fulfill the roles the lymphatic system plays in body fluid and macromolecular regulation, lipid absorption and immune function, it transports lymph from the interstitium, along the lymphatic network, through the nodes, into the great veins of the neck using contractions of the lymphatic muscle to generate and control lymph flow. However, the ionic mechanisms regulating lymphatic muscle contraction and how stretch (the predominant physical factor that regulate lymph pumping) activates them are unknown. This project will substantially advance our understanding of lymphatic biology and provide the basis for the development of therapeutic strategies to treat lymphatic contractile dysfunction, which can result in a wide range of clinical problems.
|Jafarnejad, M; Cromer, W E; Kaunas, R R et al. (2015) Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells. Am J Physiol Heart Circ Physiol 308:H697-706|
|Cromer, Walter; Wang, Wei; Zawieja, Scott D et al. (2015) Colonic Insult Impairs Lymph Flow, Increases Cellular Content of the Lymph, Alters Local Lymphatic Microenvironment, and Leads to Sustained Inflammation in the Rat Ileum. Inflamm Bowel Dis 21:1553-63|
|Kornuta, Jeffrey A; Nepiyushchikh, Zhanna; Gasheva, Olga Y et al. (2015) Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels. Am J Physiol Regul Integr Comp Physiol 309:R1122-34|
|Liao, Shan; von der Weid, P Y (2015) Lymphatic system: an active pathway for immune protection. Semin Cell Dev Biol 38:83-9|
|Chakraborty, Sanjukta; Zawieja, David C; Davis, Michael J et al. (2015) MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation. Am J Physiol Cell Physiol 309:C680-92|
|Al-Kofahi, M; Becker, F; Gavins, F N E et al. (2015) IL-1Î² reduces tonic contraction of mesenteric lymphatic muscle cells, with the involvement of cycloxygenase-2 and prostaglandin E2. Br J Pharmacol 172:4038-51|
|Kuan, Emma L; Ivanov, Stoyan; Bridenbaugh, Eric A et al. (2015) Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells. J Immunol 194:5200-10|
|Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian et al. (2015) Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance. Aging Cell 14:582-94|
|Jafarnejad, Mohammad; Woodruff, Matthew C; Zawieja, David C et al. (2015) Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes. Lymphat Res Biol 13:234-47|
|Wilson, John T; van Loon, Raoul; Wang, Wei et al. (2015) Determining the combined effect of the lymphatic valve leaflets and sinus on resistance to forward flow. J Biomech 48:3584-90|
Showing the most recent 10 out of 27 publications