Neutrophil mediated remote organ injury after lower torso ischemia and reperfusion is selectin and complement dependent.
BACKGROUND
Lower torso ischemia and reperfusion leads to remote organ leukosequestration and injury. We now examine the intermediary role of selectins and complement in mediating lung and liver injury after hindlimb ischemia.


METHODS
Mice underwent a 2-hour bilateral tourniquet hind-limb ischemia followed by 3 hours of reperfusion.


RESULTS
Neutrophil depletion significantly decreased lung vascular permeability index (PI), measured by the extravasation of 125I-albumin, and liver injury as assessed by serum alanine aminotransferse levels. Lung PI and serum alanine aminotransferse levels were also reduced in mice treated with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein. Complement inhibition with soluble complement receptor type 1 decreased lung PI and serum alanine aminotransferse levels. C5-deficient mice exhibited a similar decrease in lung PI and liver injury. Lung and liver injury were restored in C5-deficient mice reconstituted with wild-type serum.


CONCLUSIONS
Remote organ injury after lower torso reperfusion is selectin and complement dependent.
Kyriakides
C
C
Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Austen
W G
WG
Wang
Y
Y
Favuzza
J
J
Moore
F D
FD
Hechtman
H B
HB
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002199:Capillary Permeability; D003182:Complement C5 / Q000172:deficiency*; D003165:Complement System Proteins / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009102:Multiple Organ Failure / Q000209:etiology* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000097:blood; D011951:Receptors, Complement / Q000276:immunology; D015427:Reperfusion Injury / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D019087:Selectins / Q000097:blood / Q000187:drug effects / Q000276:immunology*
D003182:Complement C5; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011951:Receptors, Complement; D019087:Selectins; D003165:Complement System Proteins; D009195:Peroxidase; D000410:Alanine Transaminase