Publication Date:
1999-07-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, J -- Kim, L J -- Mealey, R -- Marsh, H C Jr -- Zhang, Y -- Tenner, A J -- Connolly, E S Jr -- Pinsky, D J -- R01 HL55397/HL/NHLBI NIH HHS/ -- R01 HL59488/HL/NHLBI NIH HHS/ -- R01 NS35144/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Jul 23;285(5427):595-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10417391" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blood Platelets/physiology
;
Cell Adhesion
;
Cerebral Cortex/blood supply/immunology/metabolism
;
Cerebral Infarction/drug therapy
;
Cerebrovascular Circulation
;
Cerebrovascular Disorders/*drug therapy/immunology/physiopathology
;
Complement Activation
;
Complement C1q/metabolism
;
Glycosylation
;
Humans
;
Ischemic Attack, Transient/*drug therapy/immunology/physiopathology
;
Leukocytes/physiology
;
Mice
;
Neurons/immunology/metabolism
;
Neuroprotective Agents/administration & dosage/adverse
;
effects/metabolism/*therapeutic use
;
Neutrophils/physiology
;
Oligosaccharides/administration & dosage/adverse effects/metabolism/*therapeutic
;
use
;
Platelet Adhesiveness
;
Receptors, Complement/administration & dosage/metabolism/*therapeutic use
;
Reperfusion Injury/drug therapy/immunology/metabolism
;
Selectins/metabolism
;
Time Factors
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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