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COMPOSITIONS AND METHODS FOR REGULATING LEUKOCYTE ADHESION
专利权人:
发明人:
Brant E. Isakson
申请号:
US15746484
公开号:
US20180207238A1
申请日:
2016.07.29
申请国别(地区):
US
年份:
2018
代理人:
摘要:
Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by many signaling processes influencing cell-to-cell interactions between vascular endothelial cells (EC) in post-capillary venules and circulating leukocytes. Here we report that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by tumor necrosis factor α (TNF α). This process involves activation of Type 1 TNF receptors, recruitment of Src Family Kinases (SFK), and SFK-dependent phosphorylation of Panx1. We report a previously unidentified role for Panx1 channels in promoting leukocyte adhesion and emigration through the venous wall during acute systemic inflammation. The present application further discloses that Panx IL2 peptide consisting of amino acid sequence KYPIVEQYLKYGRKKQRR (SEQ ID NO: 3) or 10Panx1 peptide consisting of amino acid sequence WRQAAFVDSY (SEQ ID NO: 8) are inhibitors of leukocyte adhesion.
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