Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40-CD40L system.
The vascular effects of nitrolinoleate (LNO2), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO2 was capable to deliver free radical nitric oxide (*NO) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO2 for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO2 were observed in vivo by intravital microscopy assays. LNO2 decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO2 reduced mRNA and protein expression of beta2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO2 on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO2 involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO2 inhibited adhesion molecules expression and promoted *NO inactivation of the CD40-CD40L system, both important processes of the inflammatory response.
Faine
Luciane A
LA
Faculty of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, Brazil.
Cavalcanti
Danielle M H
DM
Rudnicki
Martina
M
Ferderbar
Simone
S
Macedo
Sandra M D
SM
Souza
Heraldo P
HP
Farsky
Sandra H P
SH
Boscá
Lisardo
L
Abdalla
Dulcineia Saes Parra
DS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008041:Linoleic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D018715:Microscopy, Video / Q000379:methods; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D015538:Nitrosation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014699:Venules / Q000378:metabolism
C501855:10-nitro-9,12-octadecadienoic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D008041:Linoleic Acids; D009574:Nitro Compounds; D012333:RNA, Messenger; D023201:CD40 Ligand; D009569:Nitric Oxide