Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein

Science. 1999 Jul 23;285(5427):595-9. doi: 10.1126/science.285.5427.595.

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Platelets / physiology
  • Cell Adhesion
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / immunology
  • Cerebral Cortex / metabolism
  • Cerebral Infarction / drug therapy
  • Cerebrovascular Circulation
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / immunology
  • Cerebrovascular Disorders / physiopathology
  • Complement Activation
  • Complement C1q / metabolism
  • Glycosylation
  • Humans
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / immunology
  • Ischemic Attack, Transient / physiopathology
  • Leukocytes / physiology
  • Mice
  • Neurons / immunology
  • Neurons / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Neutrophils / physiology
  • Oligosaccharides / administration & dosage
  • Oligosaccharides / adverse effects
  • Oligosaccharides / metabolism
  • Oligosaccharides / therapeutic use*
  • Platelet Adhesiveness
  • Receptors, Complement / administration & dosage
  • Receptors, Complement / metabolism
  • Receptors, Complement / therapeutic use*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / immunology
  • Reperfusion Injury / metabolism
  • Selectins / metabolism
  • Sialyl Lewis X Antigen
  • Time Factors

Substances

  • Neuroprotective Agents
  • Oligosaccharides
  • Receptors, Complement
  • Selectins
  • Sialyl Lewis X Antigen
  • soluble complement inhibitor 1
  • Complement C1q