Published online before print January 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0703358v1 75/5/828    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garlichs, C. D. Articles by Daniel, W. G. Search for Related Content PubMed PubMed Citation Articles by Garlichs, C. D. Articles by Daniel, W. G.

(Journal of Leukocyte Biology. 2004;75:828-835.)
© 2004 by Society for Leukocyte Biology

Delay of neutrophil apoptosis in acute coronary syndromes

C. D. Garlichs^*,1,2, S. Eskafi^*,1, I. Cicha^*, A. Schmeisser, B. Walzog, D. Raaz^*, C. Stumpf^*, A. Yilmaz^*, J. Bremer^*, J. Ludwig^* and W. G. Daniel^*

^* Medical Clinic II, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany;
Heart Center, Dresden, Germany; and
Department of Physiology, Ludwig-Maximilians-University, Munich, Germany

²Correspondence: Medical Clinic II, Friedrich-Alexander-University of Erlangen-Nürnberg, c/o David-Morgenstern-Weg 14, 91056 Erlangen, Germany. E-mail: Christoph.Garlichs{at}rzmail.uni-erlangen.de

Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2±12.6%; SAP, 44.9±13.6%; UAP, 28.4±10.1%; AMI, 20.3±8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients’ sera revealed significantly elevated concentrations of tumor necrosis factor , interferon- (IFN-), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1ß in ACS (vs. C and SAP). IFN-, GM-CSF, and IL-1ß significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-, GM-CSF, and IL-1ß and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.

Key Words: inflammation • unstable angina • acute myocardial infarction • leukocytes

This article has been cited by other articles:

				I. Tracchi, G. Ghigliotti, M. Mura, S. Garibaldi, P. Spallarossa, C. Barisione, V. Boasi, M. Brunelli, L. Corsiglia, A. Barsotti, et al. Increased neutrophil lifespan in patients with congestive heart failure Eur J Heart Fail, April 1, 2009; 11(4): 378 - 385. [Abstract] [Full Text] [PDF]

				A. Farsetti, A. Grasselli, S. Bacchetti, C. Gaetano, and M. C. Capogrossi The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling J Appl Physiol, January 1, 2009; 106(1): 333 - 337. [Abstract] [Full Text] [PDF]

				D. El Kebir, L. Jozsef, and J. G. Filep Opposing regulation of neutrophil apoptosis through the formyl peptide receptor-like 1/lipoxin A4 receptor: implications for resolution of inflammation J. Leukoc. Biol., September 1, 2008; 84(3): 600 - 606. [Abstract] [Full Text] [PDF]

				E. Pluskota, D. A. Soloviev, D. Szpak, C. Weber, and E. F. Plow Neutrophil Apoptosis: Selective Regulation by Different Ligands of Integrin {alpha}M{beta}2 J. Immunol., September 1, 2008; 181(5): 3609 - 3619. [Abstract] [Full Text] [PDF]

				D. El Kebir, L. Jozsef, W. Pan, and J. G. Filep Myeloperoxidase Delays Neutrophil Apoptosis Through CD11b/CD18 Integrins and Prolongs Inflammation Circ. Res., August 15, 2008; 103(4): 352 - 359. [Abstract] [Full Text] [PDF]

				L. Dyugovskaya, A. Polyakov, P. Lavie, and L. Lavie Delayed Neutrophil Apoptosis in Patients with Sleep Apnea Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 544 - 554. [Abstract] [Full Text] [PDF]

				M. L. Narducci, A. Grasselli, L. M. Biasucci, A. Farsetti, A. Mule, G. Liuzzo, G. La Torre, G. Niccoli, R. Mongiardo, A. Pontecorvi, et al. High Telomerase Activity in Neutrophils From Unstable Coronary Plaques J. Am. Coll. Cardiol., December 18, 2007; 50(25): 2369 - 2374. [Abstract] [Full Text] [PDF]

				S. A. Madsen-Bouterse, G. J. M. Rosa, and J. L. Burton Glucocorticoid Modulation of Bcl-2 Family Members A1 and Bak during Delayed Spontaneous Apoptosis of Bovine Blood Neutrophils Endocrinology, August 1, 2006; 147(8): 3826 - 3834. [Abstract] [Full Text] [PDF]

				P. Boutet, D. Boulanger, L. Gillet, A. Vanderplasschen, R. Closset, F. Bureau, and P. Lekeux Delayed Neutrophil Apoptosis in Bovine Subclinical Mastitis J Dairy Sci, December 1, 2004; 87(12): 4104 - 4114. [Abstract] [Full Text] [PDF]