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

Judy Huang; Louis J. Kim; Richard Mealey; Henry C. Marsh; Yuan Zhang; Andrea J. Tenner; E. Sander Connolly; David J. Pinsky

doi:10.1126/science.285.5427.595

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

Judy Huang, Louis J. Kim, Richard Mealey, Henry C. Marsh, Yuan Zhang, Andrea J. Tenner, E. Sander Connolly, David J. Pinsky

Research output: Contribution to journal › Article › peer-review

285 Scopus citations

Abstract

Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit complement 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 cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.

Original language	English (US)
Pages (from-to)	595-599
Number of pages	5
Journal	Science
Volume	285
Issue number	5427
DOIs	https://doi.org/10.1126/science.285.5427.595
State	Published - Jul 23 1999
Externally published	Yes

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title = "Neuronal protection in stroke by an sLe(x)-glycosylated complement inhibitory protein",

abstract = "Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit complement 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 cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.",

author = "Judy Huang and Kim, {Louis J.} and Richard Mealey and Marsh, {Henry C.} and Yuan Zhang and Tenner, {Andrea J.} and Connolly, {E. Sander} and Pinsky, {David J.}",

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T1 - Neuronal protection in stroke by an sLe(x)-glycosylated complement inhibitory protein

AU - Huang, Judy

AU - Kim, Louis J.

AU - Mealey, Richard

AU - Marsh, Henry C.

AU - Zhang, Yuan

AU - Tenner, Andrea J.

AU - Connolly, E. Sander

AU - Pinsky, David J.

PY - 1999/7/23

Y1 - 1999/7/23

N2 - Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit complement 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 cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.

AB - Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit complement 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 cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.

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

Abstract

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