Objective: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation. Methods: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions. Results: There was a highly significant (p < 0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) ± SD, 210 ± 102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159 ± 73). Similar results were observed on the monocytes: 309 ± 151 and 235 ± 97, respectively (p < 0.00001). Conclusion: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals.

Ernst E, Hammerschmidt DE, Bagge U, Matrai A, Dormandy JA: Leukocytes and the risk of ischemic diseases. JAMA 1987;257:2318–2324.
Kannel WB, Anderson K, Wilson PW: White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA 1992;267:1253–1256.
Prentice RL, Szatrowski TP, Kato H, Mason MW: Leukocyte counts and cerebrovascular disease. J Chronic Dis 1982;35:703–714.
Ross R: Atherosclerosis – An inflammatory disease. N Engl J Med 1999;340:115–126.
Mehta JL, Saldeen TG, Rand K: Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol 1998;31:1217–1225.
Elneihoum AM, Falke P, Axelsson L, Lundberg E, Lindgarde F, Ohlsson K: Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke 1996;27:1734–1738.
Meisel SR, Shapiro H, Radnay J, Neuman Y, Khaskia AR, Gruener N, Pauzner H, David D: Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: Possible implications for leukocyte aggregation and microvascular plugging. J Am Coll Cardiol 1998;31:120–125.
Arai M, Lefer DJ, So T, DiPaula A, Aversano T, Becker LC: An anti-CD18 antibody limits infarct size and preserves left ventricular function in dogs with ischemia and 48-hour reperfusion. J Am Coll Cardiol 1996;27:1278–1285.
Sawa Y, Taniguchi K, Kadoba K, Nishimura M, Ichikawa H, Amemiya A, Kuratani T, Matsuda H: Leukocyte depletion attenuates reperfusion injury in patients with left ventricular hypertrophy. Circulation 1996;93:1640–1646.
Kumar A, Villani MP, Patel UK, Keith-JC J, Schaub RG: Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model. Circulation 1999;99:1363–1369.
Forsyth KD, Levinsky RJ: Preparative procedures of cooling and re-warming increase leukocyte integrin expression and function on neutrophils. J Immunol Methods 1990;128:159–163.
Braunwald E: Unstable angina: An etiologic approach to management. Circulation 1998;98:2219–2222.
Chopp M, Zhang ZG: Anti-adhesion molecule and nitric oxide protection strategies in ischemic stroke. Curr Opin Neurol 1996;9:68–72.
Mazzone A, De-Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, Bramucci E, Angoli L, Marsico F, Specchia G: Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 1993;88:358–363.
De-Servi S, Mazzone A, Ricevuti G, Mazzucchelli I, Fossati G, Gritti D, Angoli L, Specchia G: Clinical and angiographic correlates of leukocyte activation in unstable angina. J Am Coll Cardiol 1995;26:1146–1150.
Frenette PS, Wagner DD: Adhesion molecules – Part 1. N Engl J Med 1996;334:1526–1529.
Frenette PS, Wagner DD: Adhesion molecules – Part II: Blood vessels and blood cells. N Engl J Med 1996;335:43–45.
Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 1989;320:365–376.
Harlan JM: Leukocyte-endothelial interactions. Blood 1985;65:513–525.
Al-Saady NM, Leatham EW, Kwan JTC, Eastwood JB, Seymour CA: Monocyte expression of tissue factor and adhesion molecules: The link with accelerated coronary disease in patients with chronic heart failure. Heart 1999;81:134–140.
Schmid-Schonbein H: Blood rheology and physiology of microcirculation. Ric Clin Lab 1981;11(suppl 1):13–33.
Prestigiacomo CJ, Kim SC, Connolly S, Liao H, Yan SF, Pinsky DJ: CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke. Stroke 1999;30:1110–1117.
Soriano SG, Coxon A, Wang YF, Frosch MP, Lipton SA, Hickey PR, Mayadas TN: Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 1999;30:134–139.
Scannell G, Waxman K, Vaziri ND, Zhang J, Kaupke CJ, Jalali M, Hect C: Effects of trauma on leukocyte intercellular adhesion molecule-1, CD11b, and CD18 expressions. J Trauma 1995;39:641–644.
White-Owen C, Alexander JW, Babcock GF: Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. J Surg Res 1992;52:22–26.
White-Owen C, Hartmann S, Alexander JW, Babcock GF: Reduced PMN beta 2 integrins after trauma: A possible role for colony-stimulating factors. Clin Exp Immunol 1993;92:477–481.
Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–843.
Koenig W: Atherosclerosis involves more than just lipids: Focus on inflammation. Eur Heart J 1999;1:T19–T26.
Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB: Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349:462–466.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.