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Science 23 July 1999:
Vol. 285. no. 5427, pp. 595 - 599
DOI: 10.1126/science.285.5427.595
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Reports

Neuronal Protection in Stroke by an sLex-Glycosylated Complement Inhibitory Protein

Judy Huang, 1 Louis J. Kim, 1 Richard Mealey, 2 Henry C. Marsh Jr., 2 Yuan Zhang, 1 Andrea J. Tenner, 3 E. Sander Connolly Jr., 1 David J. Pinsky 1*

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 (sCR1sLex) to inhibit complement activation and endothelial-platelet-leukocyte interactions. sCR1 and sCR1sLex 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.

1 Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
2 Avant Immunotherapeutics, Inc., 119 Fourth Avenue, Needham, MA 02494, USA.
3 University of California, Department of Molecular Biology and Biochemistry, Irvine, CA 92697, USA.
*   To whom correspondence should be addressed. E-mail: djp5{at}columbia.edu

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