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Aging alters regulatory interactions between mast cells and mesenteric lymphatic vessels
xi, 151 leaves : illustrations (mostly color) ; 28 cm.
ABSTRACT: Aging impairs mesenteric lymph flow, which is crucial for fluid and macromolecule homeostasis, fat absorption, and immunity. Differences in contractile behavior of aged isolated mesenteric lymphatic vessels (MLV) and those observed in situ suggest an important regulatory involvement of some cellular elements in the immediate environment of aged MLV. We used whole mount immunohistochemistry (IHC) and vital staining to identify and characterize mast cells (MCs) surrounding MLV in young adult and aged Fischer-344 rats. Additionally, we investigated the aging-associated differences in MC activation in the mesenteric bed in control and treated conditions. Acute treatments of live mesenteric tissue segments with compound 48/80 and biological activators like substance P, immunoglobulin E (IgE) and peptidoglycan was performed and Ruthenium Red staining was done to identify activated MCs. The degree of activation was assessed by image analysis of activated cells in control and treated conditions. We found a greater degree of pre-activation of MCs in control conditions in aged rats compared to young adult animals. Next, we treated live mesenteric tissue isolated from Sprague Dawley, adult and aged F-344 rats for 2 hours with MC activators and performed IHC and vital dye staining to identify major histocompatibility class II (MHC II) positive cell and eosinophil localization towards MLV after MC activation. The number of immune cells near the MLV was counted and compared between treatments and ages. MCs were present at a greater density near MLV and MC activation by compound 48/80 & substance P resulted in increased localization of MHC II positive cells and eosinophils towards MLV in young adult rats. This effect was reduced in cromolyn pre-injected rats. The immune cell localization towards MLV after MC activation was reduced in aged tissues. We link these findings to our previous report of reduced numbers of intact MCs available for initiating an acute immune response in the mesentery of aged rats. These findings serve as first step in study of the aging-associated mechanisms that potentially link MCs and disordered immune function in the elderly.
"Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2013."
Approved as to style and content by: Anatoliy A. Gashev, Cynthia J. Meininger, David C. Zawieja, Pierre-Yves von der Weid, Harris J. Granger.
Ph. D. Texas A&M University System Health Science Center 2013.
Includes bibliographical references (leaves 23-44,77-86,133-141,146-147).