Moderation of skeletal muscle reperfusion injury by a sLe(x)-glycosylated complement inhibitory protein

• Published in: American Journal of Physiology: Cell Physiology 2001-07, Vol.281 (1), p.C224-C230
• Main Authors: Kyriakides, C, Wang, Y, Austen, Jr, W G, Favuzza, J, Kobzik, L, Moore, Jr, F D, Hechtman, H B
• Format: Article
• Language: English
• Subjects: Animals; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Complement Activation - drug effects; Complement Activation - physiology; Complement Inactivator Proteins - pharmacology; Hindlimb; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Neutrophils - metabolism; Oligosaccharides - metabolism; Oligosaccharides - pharmacology; Receptors, Complement - chemistry; Receptors, Complement - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Reperfusion Injury - prevention & control
• ISSN: 0363-6143
• DOI: 10.1152/ajpcell.2001.281.1.C224

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.