Recombinant soluble P-selectin glycoprotein ligand 1 moderates local and remote injuries following experimental lower-torso ischaemia

Background: A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia–reperfusion has been demonstrated by the observation that PMN depletion reduced local and remote pulmonary vascular permeability. This study investigated the role of recombinant soluble P‐selectin glyco...

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Published in:British journal of surgery 2001-06, Vol.88 (6), p.825-830
Main Authors: Kyriakides, C., Favuzza, J., Wang, Y., Austen Jr, W. G., Moore Jr, F. D., Hechtman, H. B.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Hindlimb - blood supply
Male
Medical sciences
Membrane Glycoproteins - therapeutic use
Mice
Mice, Inbred C57BL
Muscle, Skeletal - blood supply
Permeability
Peroxidase - metabolism
Reperfusion Injury - enzymology
Reperfusion Injury - prevention & control
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
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Summary:Background: A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia–reperfusion has been demonstrated by the observation that PMN depletion reduced local and remote pulmonary vascular permeability. This study investigated the role of recombinant soluble P‐selectin glycoprotein ligand–immunoglobulin fusion protein (rPSGL‐Ig), a P‐ and E‐selectin antagonist, in moderating injury. Methods: Mice underwent 2 h of hindlimb ischaemia and 3 h of reperfusion. Muscle and lung vascular permeability index (PI) was assessed by extravasation of 125I‐radiolabelled albumin. Lung myelo peroxidase (MPO) activity was also measured. Results: In mice treated with rPSGL‐Ig 1 mg/kg before reperfusion (n = 12) muscle PI was reduced by 40 per cent, whereas it was moderated by 20 per cent in animals treated 30 min after reperfusion (n = 15). Lung PI in mice treated with rPSGL‐Ig before (n = 12) and 30 min after (n = 15) reperfusion was reduced by over 99 and 98 per cent respectively. Lung MPO activity in mice treated with rPSGL‐Ig before (n = 10) and 30 min after (n = 12) reperfusion was reduced by 68 and 58 per cent respectively. Treatment with rPSGL‐Ig 1 h after reperfusion, or with m20ek.Fc 1 mg/kg (n = 9; negative control for rPSGL‐Ig which is inactive for selectin binding) before reperfusion failed significantly to moderate local or remote organ injury. Conclusion: Selectin blockade moderated local skeletal muscle and remote lung injury following hindlimb ischaemia–reperfusion. Significantly, delayed antiselectin therapy also decreased injury. © 2001 British Journal of Surgery Society Ltd
ISSN:0007-1323
1365-2168
DOI:10.1046/j.0007-1323.2001.01795.x