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US 11,331,375 B2Granted
Compositions and methods for regulating leukocyte adhesion
AssigneeUniversity of Virginia Patent Foundation
InventorBrant E. Isakson
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AssigneeUniversity of Virginia Patent Foundation
InventorBrant E. Isakson
Estimating the term…
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 RQAAFVDSY (SEQ ID NO: 8) are inhibitors of leukocyte adhesion.
A method for treating inflammation at a site of tissue injury, disease, or infection by inhibiting activation of venous endothelial cell Pannexin1, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of an inhibitor of Pannexin1 activation, thereby treating said inflammation at a site of tissue injury, disease, or infection, wherein the inhibitor of Pannexin1 activation is an Intracellular Loop 2 (IL2) peptide consisting of amino acid sequence KYPIVEQYLKYGRKKQRRR (SEQ ID NO:
A method for inhibiting inflammation and inflammatory cell recruitment at a site of tissue injury, disease, or infection wherein said inflammation and cell recruitment are associated with Pannexin1 activation in venous endothelial cells, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of an inhibitor of said venous endothelial cell Pannexin1 activation, thereby inhibiting inflammation and inflammatory cell recruitment to a site of tissue injury, disease, or infection, wherein the inhibitor of Pannexin1 activation is an Intracellular Loop 2 (IL2) peptide consisting of amino acid sequence KYPIVEQYLKYGRKKQRRR (SEQ ID NO:
A method for inhibiting TNFα-induced ATP release from a venous endothelial cell, said method comprising contacting said venous endothelial cell with an effective amount of an inhibitor of Pannexin1 activity, wherein the inhibitor of Pannexin1 activation is an Intracellular Loop 2 (IL2) peptide consisting of amino acid sequence KYPIVEQYLKYGRKKQRRR (SEQ ID NO:
Dependencies are inferred from the claim text.