Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues.

Sarit Pal,Anatoliy A Gashev,Cynthia J Meininger

doi:10.3390/ijms18050965

Sarit Pal, Anatoliy A Gashev + Show 1 more

Open Access

https://doi.org/10.3390/ijms18050965

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Abstract

This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition with a concomitant increase in permeability of aged lymphatic vessels. The contractile function of aged lymphatic vessels is depleted with the abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. In addition, aging induces oxidative stress in lymphatic vessels and facilitates the spread of pathogens from these vessels into perilymphatic tissues. Aging causes the basal activation of perilymphatic mast cells, which, in turn, restricts recruitment/activation of immune cells in perilymphatic tissues. This aging-associated basal activation of mast cells limits proper functioning of the mast cell/histamine/NF-κB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively, these changes play important roles in the pathogenesis of alterations in inflammation and immunity associated with aging.

Highlights

Lymph flow is necessary for vital functions, such as fluid and macromolecule homeostasis, absorption of lipids and transport of immune cells
We found that the permeability of aged lymphatic vessels increased in vivo, using Evans blue dye injected into the footpad of the hind limb of aged mice, as well as in ex vivo settings when fluorescently labeled bacteria were introduced into isolated, cannulated and pressurized aged rat mesenteric lymphatic vessels (MLVs) [17]
Taking into account all of these data from the literature and our experimental data [23], we proposed that aging affects the functional status of perilymphatic mast cells (MCs), which influence the contractile activity of aged lymphatic vessels as well as other lymphatic functions

Summary

Introduction

Lymph flow is necessary for vital functions, such as fluid and macromolecule homeostasis, absorption of lipids and transport of immune cells. A remarkable finding of these studies of isolated MLVs perfused with solutions containing fluorescently labeled Staphylococcus aureus was that in 9-month-old adult MLVs, bacteria had a tendency to accumulate near lymphatic valves (Figure 5k in [17]) These valvular zones, even in adult MLVs, were shown to have reduced muscle cell investiture in their walls [13]. Experiments with the injection of various fluorescently labeled microorganisms (Staphylococcus aureus, Cryptococcus neoformans, and Mycobacterium smegmatis) into the footpad of 4-month-old and 22-month-old mice, demonstrated ~100 times more bacteria accumulated in the tissues surrounding the aged lymphatic vessels than the young ones [17] These findings reinforce the observation that aging increases lymphatic vessel permeability, diminishing lymphatic vessel barrier function and compromising pathogen transport

Aging-Associated Alterations in Lymphatic Contractility and Lymph Flow

Aging-Associated Oxidative Stress in Perilymphatic Tissues

Findings

Conclusions