Effect of mast cell activation on immune cell trafficking towards mesenteric lymphatic vessels and its aging‐associated alterations

Abstract

Aging impairs mesenteric lymph flow, which is crucial for fluid and macromolecule homeostasis, fat absorption, and immune function. Previously, we had demonstrated that mast cells line mesenteric lymphatic vessels (MLV) with a greater degree of basal activation of mast cells in aged mesentery. The number of intact mast cells available to react acutely to inflammatory stimuli was decreased with age. In this study we treated live mesenteric tissue isolated from adult and aged F‐344 rats for 2 hours with mast cell activators and performed whole mount IHC and vital dye staining to identify immune cell recruitment towards MLV after mast cell activation. Number of immune cells near MLV was counted and compared between treatments and ages. With greater density of mast cells near MLV, we demonstrated that mesenteric mast cell activation by Compound 48/80 & Substance P resulted in migration of MHC II positive cells and eosinophils towards MLV. This effect was reduced in cromolyn pre‐injected rats. The immune cell recruitment towards MLV after mast cell activation was reduced in aged tissues. We link these findings to our previous report of lesser number of intact mast cells available for initiating an acute immune response in aged mesentery. These findings serve as first step in study of the aging‐associated mechanisms that potentially link mast cells and disordered immune function in the elderly. NIH R01 AG030578, HL094269.