C16 peptide shown to prevent leukocyte infiltration and alleviate detrimental inflammation in acute allergic encephalomyelitis model.
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.
Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, 866 Yuhangtang Road, 310058 Hangzhou, China. fangmaro@zju.edu.cn
Marong
M
Fang
Yayi
Y
Sun
Zhiying
Z
Hu
Jing
J
Yang
Henry
H
Davies
Beibei
B
Wang
Shucai
S
Ling
Shu
S
Han
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
D000893:Anti-Inflammatory Agents; D039302:Integrin alphaVbeta3; D007797:Laminin; D018696:Neuroprotective Agents; D010446:Peptide Fragments