Vasodilation elicited by liposomal VIP is unimpeded by anti-VIP antibody in hamster cheek pouch.
The purpose of this study was to determine whether a monoclonal anti-vasoactive intestinal peptide (VIP) antibody, which binds VIP with high affinity and specificity and catalyzes cleavage of the peptide in vitro, attenuates VIP vasorelaxation in vivo and, if so, whether insertion of VIP on the surface of sterically stabilized liposomes (SSL), which protects the peptide from trypsin- and plasma-catalyzed cleavage in vitro, curtails this response. Using intravital microscopy, we found that suffusion of monoclonal anti-VIP antibody (clone c23.5, IgG2ak), but not of nonimmune antibody (myeloma cell line UPC10, IgG2ak) or empty SSL, significantly attenuates VIP-induced vasodilation in the in situ hamster cheek pouch (P < 0.05). By contrast, anti-VIP antibody has no significant effects on vasodilation elicited by isoproterenol, nitroglycerin, and calcium ionophore A-23187, agonists that activate intracellular effector systems in blood vessels that mediate, in part, VIP vasoreactivity. Suffusion of VIP on SSL, but not of empty SSL, restores the vasorelaxant effects of VIP in the presence of anti-VIP antibody. Collectively, these data suggest that VIP catalysis by high affinity and specific VIP autoantibodies displaying protease-like activity constitutes a novel mechanism whereby VIP vasoreactivity is regulated in vivo.
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
H
H
Ikezaki
S
S
Paul
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H
Alkan-Onyüksel
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M
Patel
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XP
Gao
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Rubinstein
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002610:Cheek; D006224:Cricetinae; D004337:Drug Carriers; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009061:Mouth Mucosa / Q000098:blood supply*; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D007545:Isoproterenol