In the present work, we demonstrated that chemically different nitric oxide (NO)-releasing compounds inhibit tumor necrosis factor alpha (TNF-alpha)-induced polymorphonuclear leukocyte adhesion to endothelial cells in vitro. Two mesoionic oxatriazole derivatives GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3(3,4-dichlorophenyl)-chloride) and GEA 3175 (1,2,3,4-oxatriazolium,-3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) were compared to the earlier-known NO donor SIN-1 (3-morpholino-sydnonimine). GEA 3162 (3-10 mu M) and GEA 3175 (10-30 mu M) inhibited human polymorphonuclear leukocyte adhesion to B-4 endothelial cells in a dose-dependent manner being more potent than SIN-1. In the present model, leukocytes rather than endothelial cells seemed to be the target of the effect of NO. Flow cytometric analysis showed that NO-releasing compounds did not alter TNF-alpha induced CD11/CD18 surface expression in polymorphonuclear leukocytes. The inhibitory action of NO-releasing compounds on adhesion paralleled with the increased synthesis of cGMP in polymorphonuclear leukocytes. Analogues of cGMP inhibited polymorphonuclear leukocyte adhesion indicating a role for cGMP in the action of NO donors. The results suggest that exogenous NO in the form of NO-releasing compounds inhibits polymorphonuclear leukocyte adhesion to endothelial cells, which may be implicated in the regulation of leukocyte migration and leukocyte-mediated tissue injury. (C) 1999 Elsevier Science B.V. All rights reserved.
机构:
Univ South Australia, Future Ind Inst, Mawson Lakes, SA 5095, Australia
Univ South Australia, Sch Informat Technol & Math Sci, Mawson Lakes Campus, Mawson Lakes, SA 5095, AustraliaUNSW Australia, Sch Chem Engn, CAMD, Sydney, NSW 2052, Australia
Krasowska, Marta
Blencowe, Anton
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Univ South Australia, Future Ind Inst, Mawson Lakes, SA 5095, Australia
Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA 5000, AustraliaUNSW Australia, Sch Chem Engn, CAMD, Sydney, NSW 2052, Australia
机构:
Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
Zhou, Xin
Zhang, Jimin
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Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
Zhang, Jimin
Feng, Guowei
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Tianjin Med Univ Canc Inst & Hosp, Dept Genitourinary Oncol, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
Feng, Guowei
Shen, Jie
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Nankai Univ, Sch Pharm, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
Shen, Jie
Kong, Deling
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Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
Kong, Deling
Zhao, Qiang
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Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin 300071, Peoples R China
机构:
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United StatesDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Jae, Ho Shin
Metzger, Sara K.
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Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United StatesDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Metzger, Sara K.
Schoenfisch, Mark H.
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Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United StatesDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Schoenfisch, Mark H.
Journal of the American Chemical Society,
2007,
129
(15):
: 4612
-
4619
机构:
Univ New South Wales UNSW Sydney, Sch Chem Engn, Sydney, NSW 2052, Australia
Univ Sydney, Sch Chem & Biomol Engn, Sydney, NSW 2006, AustraliaUniv New South Wales UNSW Sydney, Sch Chem Engn, Sydney, NSW 2052, Australia
Yang, Tao
Zelikin, Alexander N.
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机构:
Aarhus Univ, Nanosci Ctr, Dept Chem, DK-8000 Aarhus C, Denmark
Aarhus Univ, iNANO Interdisciplinary Nanosci Ctr, DK-8000 Aarhus C, DenmarkUniv New South Wales UNSW Sydney, Sch Chem Engn, Sydney, NSW 2052, Australia
Zelikin, Alexander N.
Chandrawati, Rona
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Univ New South Wales UNSW Sydney, Sch Chem Engn, Sydney, NSW 2052, Australia
Univ Sydney, Sch Chem & Biomol Engn, Sydney, NSW 2006, AustraliaUniv New South Wales UNSW Sydney, Sch Chem Engn, Sydney, NSW 2052, Australia