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Heart and Vessels

, Volume 27, Issue 5, pp 468–474 | Cite as

Aminobenzoic acid hydrazide, a myeloperoxidase inhibitor, alters the adhesive properties of neutrophils isolated from acute myocardial infarction patients

  • Lili Han
  • Xiaoli Shen
  • Leng Pan
  • Saimei Lin
  • Xiaoqing Liu
  • Yulian Deng
  • Xiaodong Pu
Original Article

Abstract

Acute myocardial infarction (AMI) is associated with vascular inflammation, including activation and adherence of neutrophils to vascular endothelial cells via CD11b/CD18 intercellular adhesion molecule interactions. Myeloperoxidase (MPO) induces CD11b surface expression in polymorphonuclear neutrophils (PMNs); however, its role in regulating adhesion in AMI is not well characterized. This study investigates the effects of aminobenzoic acid hydrazide (ABAH), an inhibitor of MPO, antibodies specific for CD11b, on the adhesion of PMNs isolated from AMI patients to endothelial cells. Human neutrophils were isolated from the peripheral blood of 20 patients with AMI or 20 healthy participants as control using Percoll density gradient centrifugation. The major biochemical indicators were detected with different biochemical analyses. The effects of ABAH and anti-CD11b antibodies on neutrophil adhesion to endothelial cell were measured using adhesion assays in vitro. The adhesion rate was significantly higher for neutrophils isolated from AMI patients than healthy individuals (P < 0.001). ABAH significantly inhibited MPO activity in PMNs isolated from AMI patients. Neutrophil adhesion was significantly reduced upon treatment with 10 and 20 μM ABAH in a dose-dependent manner. Treatment with anti-CD11b antibodies also significantly reduced neutrophil adhesion in comparison with the untreated control group (P < 0.001). Thus, both ABAH and anti-CD11b antibodies reduced PMN adhesion. Further studies are necessary to determine whether MPO enhances neutrophil adhesion to endothelial cells in AMI patients through the upregulation of CD11b expression on the surface of neutrophils, which is abrogated by ABAH.

Keywords

Myeloperoxidase Aminobenzoic acid hydrazide Neutrophil Endothelial cell Adhesion rate 

Notes

Acknowledgments

This work was supported by a grant from the Nature Science Foundation of Fujian Province (2006J0326, X0650036), Scientific and Technological Planning Projects of Fujian Province (2005Q006).

Conflict of interest

None.

References

  1. 1.
    Murphy RT, Foley JB, Crean P, Walsh MJ (2003) Reciprocal activation of leukocyte-endothelial adhesion molecules in acute coronary syndromes. Int J Cardiol 90(2–3):247–252PubMedCrossRefGoogle Scholar
  2. 2.
    Derosa G, Ferrari I, D’Angelo A, Salvadeo SA, Fogari E, Gravina A, Mereu R, Palumbo I, Maffioli P, Randazzo S, Cicero AF (2009) Oral fat load effects on inflammation and endothelial stress markers in healthy subjects. Heart Vessels 24(3):204–210CrossRefGoogle Scholar
  3. 3.
    Ketonen J, Pilvi T, Mervaala E (2010) Caloric restriction reverses high-fat diet-induced endothelial dysfunction and vascular superoxide production in C57Bl/6 mice. Heart Vessels 25(3):254–262CrossRefGoogle Scholar
  4. 4.
    Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917):868–874PubMedCrossRefGoogle Scholar
  5. 5.
    Hermand P, Huet M, Callebaut I, Gane P, Ihanus E, Gahmberg CG, Cartron JP, Bailly P (2000) Binding sites of leukocyte beta 2 integrins (LFA-1, Mac-1) on the human ICAM-4/lW blood group protein. J Biol Chem 275(34):26002–26010PubMedCrossRefGoogle Scholar
  6. 6.
    Tavora FR, Ripple M, Li L, Burke AP (2009) Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques. BMC Cardiovasc Disord 9:27PubMedCrossRefGoogle Scholar
  7. 7.
    Baldus S, Heitzer T, Eiserich JP, Lau D, Mollnau H, Ortak M, Petri S, Goldmann B, Duchstein HJ, Berger J, Helmchen U, Freeman BA, Meinertz T, Münzel T (2004) Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. Free Radic Biol Med 37(6):902–911PubMedCrossRefGoogle Scholar
  8. 8.
    Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Munzel T, Simoons ML, Hamm CW (2003) Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 108(12):1440–1445PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL (2001) Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 286(17):2136–2142PubMedCrossRefGoogle Scholar
  10. 10.
    Daugherty A, Dunn JL, Rateri DL, Heinecke JW (1994) Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest 94(1):437–444PubMedCrossRefGoogle Scholar
  11. 11.
    Winterbourn CC (2002) Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous acid. Toxicology 181–182:223–227PubMedCrossRefGoogle Scholar
  12. 12.
    Lau D, Mollnau H, Eiserich JP, Freeman BA, Daiber A, Gehling UM, Brummer J, Rudolph V, Munzel T, Heitzer T, Meinertz T, Baldus S (2005) Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci USA 102(2):431–436PubMedCrossRefGoogle Scholar
  13. 13.
    Mytar B, Siedlar M, Woloszyn M, Ruggiero I, Pryjma J, Zembala M (1999) Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity. Br J Cancer 79(5–6):737–743PubMedCrossRefGoogle Scholar
  14. 14.
    Engelmann I, Dormann S, Saran M, Bauer G (2000) Transformed target cell-derived superoxide anions drive apoptosis induction by myeloperoxidase. Redox Rep 5(4):207–214PubMedCrossRefGoogle Scholar
  15. 15.
    Kettle AJ, Gedye CA, Hampton MB, Winterbourn CC (1995) Inhibition of myeloperoxidase by benzoic acid hydrazides. Biochem J 308(Pt 2):559–563PubMedGoogle Scholar
  16. 16.
    Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC Jr (2002) American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina) ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 106(14):1893–1900PubMedCrossRefGoogle Scholar
  17. 17.
    Nauck M, Warnick GR, Rifai N (2002) Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clin Chem 48(2):236–254PubMedGoogle Scholar
  18. 18.
    Lv J, Wang J, Zhang X, Zhang X (2000) Isolation of human peripheral blood neutrophil using Percoll discontinuous density gradient sedimentation. Shanghai J Immunol 20:122Google Scholar
  19. 19.
    Situ ZQ, Wu JZ (1996) Cell culture, the first edition. Word Publishing Corporation, pp 188–189Google Scholar
  20. 20.
    Packard RR, Libby P (2008) Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 54(1):24–38PubMedCrossRefGoogle Scholar
  21. 21.
    Chia S, Nagurney JT, Brown DF, Raffel OC, Bamberg F, Senatore F, Wackers FJ, Jang IK (2009) Association of leukocyte and neutrophil counts with infarct size, left ventricular function and outcomes after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiol 103(3):333–337PubMedCrossRefGoogle Scholar
  22. 22.
    Cunha TM, Verri WA Jr, Schivo IR, Napimoga MH, Parada CA, Poole S, Teixeira MM, Ferreira SH, Cunha FQ (2008) Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. J Leukoc Biol 83(4):824–832PubMedCrossRefGoogle Scholar
  23. 23.
    Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67(6):1033–1036PubMedCrossRefGoogle Scholar
  24. 24.
    Vita JA, Brennan ML, Gokce N, Mann SA, Goormastic M, Shishehbor MH, Penn MS, Keaney JF Jr, Hazen SL (2004) Serum myeloperoxidase levels independently predict endothelial dysfunction in humans. Circulation 110(9):1134–1139PubMedCrossRefGoogle Scholar
  25. 25.
    Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA (2002) Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 296(5577):2391–2394PubMedCrossRefGoogle Scholar
  26. 26.
    Panzenboeck U, Raitmayer S, Reicher H, Lindner H, Glatter O, Malle E, Sattler W (1997) Effects of reagent and enzymatically generated hypochlorite on physicochemical and metabolic properties of high density lipoproteins. J Biol Chem 272(47):29711–29720PubMedCrossRefGoogle Scholar
  27. 27.
    El Kebir D, Jozsef L, Pan W, Filep JG (2008) Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation. Circ Res 103(4):352–359PubMedCrossRefGoogle Scholar
  28. 28.
    Kuligowski MP, Kwan RY, Lo C, Wong C, James WG, Bourges D, Ooi JD, Abeynaike LD, Hall P, Kitching AR, Hickey MJ (2009) Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion. Blood 113(25):6485–6494PubMedCrossRefGoogle Scholar
  29. 29.
    Nolan SL, Kalia N, Nash GB, Kamel D, Heeringa P, Savage CO (2008) Mechanisms of ANCA-mediated leukocyte-endothelial cell interactions in vivo. J Am Soc Nephrol 19(5):973–984PubMedCrossRefGoogle Scholar
  30. 30.
    Kettle AJ, Gedye CA, Winterbourn CC (1997) Mechanism of inactivation of myeloperoxidase by 4-aminobenzoic acid hydrazide. Biochem J 321(Pt 2):503–508PubMedGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Lili Han
    • 1
  • Xiaoli Shen
    • 1
  • Leng Pan
    • 1
  • Saimei Lin
    • 1
  • Xiaoqing Liu
    • 1
  • Yulian Deng
    • 1
  • Xiaodong Pu
    • 1
  1. 1.Fujian Provincial Key Laboratory of Cardiovascular Disease, Affiliated Fujian Provincial HospitalFujian Medical UniversityFujianPeople’s Republic of China

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