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

A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia-reperfusion has been demonstrated by the observation that PMN de pletion reduced local and remote pulmonary vascular permeability. This stud y investigated the role of recombinant soluble P-selectin glycoprotein liga nd-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist , in moderating injury. Mice underwent 2 h of hindlimb ischaemia and 3 h of reperfusion. Muscle and lung vascular permeability index (PI) was assessed by extravasation of I-1 25-radiolabelled albumin. Lung myelo peroxidase (MPO) activity was also mea sured. 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 ani mals treated 30 min after reperfusion (n = 15). Lung PI in mice treated wit h rPSGL-Ig before (n = 12) and 30 min after (n = 15) reperfusion was reduce d by over 99 and 98 per cent respectively. Lung MPO activity in mice treate d with rPSGL-Ig before (n = 10) and 30 min after (n = 12) reperfusion was r educed by 68 and 58 per cent respectively. Treatment with rPSGL-Ig 1 h afte r reperfusion, or with m20ek.Fc 1 mg/kg (n = 9; negative control for rPSGL- Ig which is inactive for selectin binding) before reperfusion failed signif icantly to moderate local or remote organ injury. Selectin blockade moderated local skeletal muscle and remote lung injury fo llowing hindlimb ischaemia-reperfusion. Significantly, delayed antiselectin therapy also decreased injury.