Neuronal protection in stroke by an sLe(x)-glycosylated complement inhibitory protein

Glycoprotein adhesion receptors such as selectins contribute to tissue inju ry in stroke. Ischemic neurons strongly expressed C1q, which may target the m for complement-mediated attack or C1qRp-mediated clearance. A hybrid mole cule was used to simultaneously inhibit both complement activation and sele ctin-mediated adhesion. The extracellular domain of soluble complement rece ptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit compl ement activation and endothelial-platelet-Leukocyte interactions. sCR1 and sCR1sLe(x) colocalized to ischemic cerebral microvessels and C1q-expressing neurons, inhibited neutrophil and platelet accumulation, and reduced cereb ral infarct volumes. Additional benefit was conferred by sialyl Lewis x gly cosylation of the unmodified parent sCR1 molecule.