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