title: Antibody blockade of mucosal addressin cell adhesion molecule-1 attenuates proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These findings demonstrate that antibody blockade of MAdCAM-1 attenuates the proinflammatory activity of mesenteric lymph after HS/R.
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Wuhan, China; Tongji Medical College and Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhanghongyidoc@foxmail.com.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH.
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Wuhan, China; Tongji Medical College and Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jie-Xiong
authors.initials: JX
authors.lastname: Feng
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D007155:Immunologic Factors / Q000627:therapeutic use*; D007422:Intestines / Q000276:immunology* / Q000503:physiopathology; D008196:Lymph / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008643:Mesentery / Q000276:immunology*; D009088:Mucoproteins / Q000276:immunology* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D007136:Immunoglobulins; D007155:Immunologic Factors; C504268:Madcam1 protein, rat; D009088:Mucoproteins