Apolipoprotein A-IV inhibits experimental colitis.
The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined this possibility in a mouse model of acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) in their drinking water for 7 days, with or without daily intraperitoneal injections of recombinant human apoA-IV. apoA-IV significantly and specifically delayed the onset, and reduced the severity and extent of, DSS-induced inflammation, as assessed by clinical disease activity score, macroscopic appearance and histology of the colon, and tissue myeloperoxidase activity. Intravital fluorescence microscopy of colonic microvasculature revealed that apoA-IV significantly inhibited DSS-induced leukocyte and platelet adhesive interactions. Furthermore, apoA-IV dramatically reduced the upregulation of P-selectin on colonic endothelium during DSS-colitis. apoA-IV knockout mice exhibited a significantly greater inflammatory response to DSS than did their WT littermates; this greater susceptibility to DSS-induced inflammation was reversed upon exogenous administration of apoA-IV to knockout mice. These results provide the first direct support for the hypothesis that apoA-IV is an endogenous anti-inflammatory protein. This anti-inflammatory effect likely involves the inhibition of P-selectin-mediated leukocyte and platelet adhesive interactions.
Vowinkel
Thorsten
T
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA.
Mori
Mikiji
M
Krieglstein
Christian F
CF
Russell
Janice
J
Saijo
Fumito
F
Bharwani
Sulaiman
S
Turnage
Richard H
RH
Davidson
W Sean
WS
Tso
Patrick
P
Granger
D Neil
DN
Kalogeris
Theodore J
TJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism*; D001054:Apolipoproteins A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000033:anatomy & histology / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000633:toxicity; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001054:Apolipoproteins A; D007202:Indicators and Reagents; D019007:P-Selectin; D011994:Recombinant Proteins; C022205:apolipoprotein A-IV; D016264:Dextran Sulfate