Mast cell-directed recruitment of MHC class II positive cells and eosinophils towards mesenteric lymphatic vessels in adulthood and elderly.

BACKGROUND

Aging impairs mesenteric lymph flow, which is crucial for fluid and macromolecule homeostasis, fat absorption, and immune function. Previously, we demonstrated that mast cells (MCs) line mesenteric lymphatic vessels (MLVs) with a greater degree of basal activation of MCs in aged mesentery. The number of intact MCs available to react acutely to inflammatory stimuli was decreased with age. However, the role of mast cells in recruiting other immune cells towards MLVs and its aging-associated alterations has not been explored before in great detail.

METHODS AND RESULTS

In this study we treated live mesenteric tissue isolated from Sprague Dawley (SD) rats, as well as adult 9-mo and aged 24-mo Fischer-344 (F-344) rats for 2 hours with MC activators (48/80 and Substance P) and performed whole mount IHC and vital dye staining of the mesenteric segments containing MLVs to identify immune cell recruitment towards MLVs after mast cell (MC) activation. Number of major histocompatibility complex (MHC) class II positive APCs and eosinophils near MLVs was counted and compared between treatments and ages.

CONCLUSIONS

With greater density of MCs near MLVs, we for the first time demonstrated that mesenteric MC activation by compound 48/80 and Substance P resulted in recruitment of MHC class II positive cells and eosinophils towards MLVs. This effect was reduced in cromolyn-injected rats, thus confirming that MCs are necessary for such recruitment. The immune cell presence near MLVs after MC activation was reduced in aged tissues. We link these findings to our previous report of lesser number of intact MCs available for initiating an acute immune response in aged mesentery. Cumulatively, these findings serve as the first step in study of the aging-associated mechanisms that link MCs, lymphatic vessels, and disordered immune function in the elderly.