C16 peptide shown to prevent leukocyte infiltration and alleviate detrimental inflammation in acute allergic encephalomyelitis model.

Abstract

Integrins are important adhesion receptors for leukocytes binding to endothelial cellular adhesion molecules. Previous studies have suggested that blocking relevant integrins might prevent leukocyte infiltration and suppress clinical and pathological features of neuroinflammatory disease. Experimental autoimmune encephalomyelitis (EAE), a rodent model of Multiple sclerosis (MS), is characterized by chronic inflammatory disorder of the central nervous system in which circulating leukocytes enter the brain and spinal cord leading to inflammation, myelin damage and subsequent paralysis. To prove this hypothesis and explore a promising application for MS treatment, the effects of C16, an ανβ3 integrin-binding peptide, were tested in vitro and in vivo by transendothelial assay, electron microscopy observation, multiple histological and immunohistochemical staining. The results showed C16 inhibited transendothelial migration of the C8166-CD4 lymphoblast cells, and alleviated extensive spinal cord and brain infiltration of leukocytes and macrophages in the EAE model. Furthermore, a significant amelioration of astrogliosis and a dramatic decrease in demyelination and axonal loss were observed in C16 treated animals. The attenuating inflammatory progression may improve the regional environment and trigger further neuroprotective effects on myelin and axons, all this suggests that C16 peptide may be a promising therapeutic agent for multiple sclerosis.

• Authors: Marong Fang, Yayi Sun, Zhiying Hu, Jing Yang, Henry Davies, Beibei Wang, Shucai Ling, Shu Han
• Journal: Neuropharmacology (Neuropharmacology) Vol. 70 Pg. 83-99 (Jul 2013) ISSN: 1873-7064 [Electronic] England
• PMID: 23352465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Integrin alphaVbeta3
• Laminin
• Neuroprotective Agents
• Peptide Fragments

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Movement (drug effects)
• Central Nervous System (drug effects, pathology)
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, pathology)
• Human Umbilical Vein Endothelial Cells
• Humans
• Inflammation (drug therapy, pathology)
• Integrin alphaVbeta3 (antagonists & inhibitors, metabolism)
• Laminin (pharmacology, therapeutic use)
• Leukocytes (drug effects)
• Lymphocytes (drug effects)
• Macrophages (drug effects)
• Male
• Nerve Degeneration (pathology)
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (pharmacology, therapeutic use)
• Rats