Murine model of gastrointestinal ischemia associated with complement-dependent injury.
Gastrointestinal ischemia-reperfusion (I/R) injury is often associated with remote tissue injury. Complement activation plays an important role in local and remote tissue injury associated with gastrointestinal I/R. We developed a new murine model of gastrointestinal I/R that has complement-dependent local and remote tissue injury. Twenty, but not thirty, minutes of gastrointestinal ischemia followed by 3 h of reperfusion induced a significant loss of intestinal lactate dehydrogenase that was significantly prevented by a murine anti-murine C5 monoclonal antibody. Anti-C5 also significantly decreased neutrophil infiltration into the gut and lung. Gastrointestinal I/R significantly increased pulmonary intercellular adhesion molecule-1 mRNA and protein expression that was significantly inhibited by anti-C5. Pulmonary macrophage inflammatory protein-2 mRNA was significantly induced by gastrointestinal I/R and inhibited by anti-C5 treatment. These data demonstrate that brief periods of murine gastrointestinal I/R activate complement, leading to tissue injury and neutrophil accumulation. Anti-C5 treatment attenuates tissue injury, neutrophil recruitment, and leukocyte adherence molecule and chemokine expression in the mouse. This model will be well suited to investigate the role of complement-mediated tissue injury and gene expression after gastrointestinal I/R.
Zhao
Hui
H
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Montalto
Michael C
MC
Pfeiffer
Kristine J
KJ
Hao
Liming
L
Stahl
Gregory L
GL
D000818:Animals; D004396:Coloring Agents; D003182:Complement C5 / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000502:physiology*; D004064:Digestive System / Q000098:blood supply* / Q000473:pathology*; D005767:Gastrointestinal Diseases / Q000503:physiopathology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007422:Intestines / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004396:Coloring Agents; D003182:Complement C5; D018799:Intercellular Adhesion Molecule-1; D003165:Complement System Proteins; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase