Antibody blockade of mucosal addressin cell adhesion molecule-1 attenuates proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation

Abstract

The current study was designed to determine the effects of antibody blockade of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on the proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation (HS/R). Rats were subjected to HS/R with or without treatment with MAdCAM-1 polyclonal antibody. MAdCAM-1 expression and lymphocyte infiltration in rats were examined. Post-shock mesenteric lymph was collected, filtered to remove lymphocytes, and transfused into recipient mice to induce systemic inflammation and intestinal injury. The proinflammatory activity of post-shock lymph in mice was determined by examining intestinal permeability, enterocyte apoptosis, intestinal lactate levels, lung myeloperoxidase (MPO) activity, and serum cytokine levels. Survival of recipient mice was determined over a 1-week time period. Rats subjected to HS/R had increased MAdCAM-1 expression and lymphocyte infiltration in the intestine. Antibody blockade of MAdCAM-1 attenuated the increased lymphocyte infiltration after HS/R (P < .05). Post-shock mesenteric lymph transfusion significantly increased mortality accompanied by increases in gut permeability, enterocyte apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor-β (all P < .05). Antibody blockade of MAdCAM-1 in rats subjected to HS/R attenuated the proinflammatory activity of post-shock mesenteric lymph, with abrogation of lymph transfusion-induced increases in mortality, gut permeability, epithelial cell apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of IL-1β, IL-6, and TNF-α (all P < .05). These findings demonstrate that antibody blockade of MAdCAM-1 attenuates the proinflammatory activity of mesenteric lymph after HS/R.