Moderation of skeletal muscle reperfusion injury by a sLe(x)-glycosylated complement inhibitory protein.
The role of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating skeletal muscle reperfusion injury, by antagonizing neutrophil endothelial selectin interaction and complement activation, is examined. Mice underwent 2 h of hindlimb ischemia and 3 h of reperfusion. Permeability index (PI) was assessed by extravasation of 125I-labeled albumin. Neutrophil depletion and complement inhibition with sCR1 reduced permeability by 72% (PI 0.81 +/- 0.10) compared with a 42% decrease (PI 1.53 +/- 0.08) observed in neutropenic mice, indicating that part of the complement-mediated injury is neutrophil independent. sCR1sLe(x) treatment reduced PI by 70% (PI 0.86 +/- 0.06), an additional 20% decrease compared with sCR1 treatment (PI 1.32 +/- 0.08). Treatment with sCR1sLe(x) 0.5 and 1 h after reperfusion reduced permeability by 63% (PI 0.09 +/- 0.07) and 52% (PI 1.24 +/- 0.09), respectively, compared with the respective decreases of 41% (PI 1.41 +/- 0.10) and 32% (PI 1.61 +/- 0.07) after sCR1 treatment. Muscle immunohistochemistry stained for sCR1 only on the vascular endothelium of sCR1sLe(x)-treated mice. In conclusion, sCR1sLe(x) is more effective than sCR1 in moderating skeletal muscle reperfusion injury.
Kyriakides
C
C
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Wang
Y
Y
Austen
W G
WG
Favuzza
J
J
Kobzik
L
L
Moore
F D
FD
Hechtman
H B
HB
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D006614:Hindlimb; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology*; D011951:Receptors, Complement / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D000080506:Sialyl Lewis X Antigen
D003169:Complement Inactivator Proteins; D009844:Oligosaccharides; D011951:Receptors, Complement; D011994:Recombinant Proteins; D000080506:Sialyl Lewis X Antigen; C082885:soluble complement inhibitor 1