This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Maria F. Jimenez, MD; R. William G. Watson, PhD; Jean Parodo; David Evans, MD; Debra Foster, RN; Marilyn Steinberg, RN; Ori D. Rotstein, MD; John C. Marshall, MD

Arch Surg. 1997;132(12):1263-1270.

Abstract
Objective
To study the effect of the systemic inflammatory response syndrome (SIRS) or major elective surgery on the apoptosis of circulating polymorphonuclear neutrophils because an activated inflammatory response is terminated, in part, through the programmed cell death, or apoptosis, of its effector cells.

Design
A prospective inception cohort study.

Setting
A mixed surgical and medical intensive care unit of an adult tertiary care hospital.

Patients
Sixteen patients with SIRS, 7 uninfected patients who had undergone elective aortic aneurysmectomy, and 8 healthy laboratory control subjects.

Interventions
Serial blood samples were drawn for evaluation of neutrophil apoptosis, activational state, and surface receptor expression by flow cytometry.

Main Outcome Measures
Spontaneous apoptosis was significantly delayed in neutrophils from patients with SIRS (8.6%±6.8%) and patients who had undergone elective aortic aneurysmectomy (11.0%±5.0%) when compared with controls (34.9%±6.8%). These neutrophils were activated as evidenced by enhanced respiratory burst activity and augmented surface expression of CD11b. Apoptosis in response to engagement of cell surface Fas (also known as CD95 or APO-1) with an agonistic antibody was blunted. Plasma from patients with SIRS or patients who had undergone elective aortic aneurysmectomy suppressed the apoptotic responses of control neutrophils (plasma from patients with SIRS, 18.8%±10.3%; plasma from patients who had undergone elective aortic aneurysmectomy, 20.0%±6.1%; P<.01). Western blot analysis showed normal expression of the key proapoptotic proteases, interleukin 1 β converting enzyme and CPP32 (also known as YAMA, apopain, and caspase 3), indicating that delayed apoptosis was not a consequence of decreased levels of proapoptotic enzymes.

Conclusions
Circulating neutrophils from patients with SIRS or from patients who have undergone major elective surgery show delayed expression of constitutive programmed cell death, and antiapoptotic factors are present in the general circulation. While prolonged neutrophil survival may represent an appropriate adaptive response to injury, the presence of activated and apoptosis-resistant cells in an antiapoptotic environment may contribute to the systemic inflammatory injury characteristic of SIRS and predispose to the development of the multiple organ dysfunction syndrome.

Arch Surg. 1997;132:1263-1270

Author Affiliations
From the Department of Surgery, University of Toronto, and the Medical/Surgical Intensive Care Unit, the Toronto Hospital, Toronto, Ontario.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Delayed neutrophil apoptosis in patients with unstable angina: relation to C-reactive protein and recurrence of instability
Biasucci et al.
Eur Heart J 2009;30:2220-2225.
ABSTRACT | FULL TEXT  

Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity
Luk et al.
J. Leukoc. Biol. 2008;83:804-816.
ABSTRACT | FULL TEXT  

Dynamic Regulation of Neutrophil Survival through Tyrosine Phosphorylation or Dephosphorylation of Caspase-8
Jia et al.
J. Biol. Chem. 2008;283:5402-5413.
ABSTRACT | FULL TEXT  

Simvastatin Increases Neutrophil Apoptosis and Reduces Inflammatory Reaction After Coronary Surgery
Chello et al.
Ann. Thorac. Surg. 2007;83:1374-1380.
ABSTRACT | FULL TEXT  

Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of {delta}-PKC and ERK1/2
Kilpatrick et al.
J. Leukoc. Biol. 2006;80:1512-1521.
ABSTRACT | FULL TEXT  

In vivo regulation of neutrophil apoptosis by C5a during sepsis
Guo et al.
J. Leukoc. Biol. 2006;80:1575-1583.
ABSTRACT | FULL TEXT  

Aminopeptidase N (CD13) Regulates Tumor Necrosis Factor-{alpha}-induced Apoptosis in Human Neutrophils
Cowburn et al.
J. Biol. Chem. 2006;281:12458-12467.
ABSTRACT | FULL TEXT  

Chemokine- and adhesion-dependent survival of neutrophils after transmigration through cytokine-stimulated endothelium
McGettrick et al.
J. Leukoc. Biol. 2006;79:779-788.
ABSTRACT | FULL TEXT  

An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X7.
Nagaoka et al.
J. Immunol. 2006;176:3044-3052.
ABSTRACT | FULL TEXT  

The role and regulation of apoptosis in sepsis
Wesche-Soldato et al.
Innate Immunity 2005;11:375-382.
ABSTRACT  

Leukocyte apoptosis and its significance in sepsis and shock
Wesche et al.
J. Leukoc. Biol. 2005;78:325-337.
ABSTRACT | FULL TEXT  

Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C
Kotone-Miyahara et al.
J. Leukoc. Biol. 2004;76:1047-1056.
ABSTRACT | FULL TEXT  

Selective regulation by {delta}-PKC and PI 3-kinase in the assembly of the antiapoptotic TNFR-1 signaling complex in neutrophils
Kilpatrick et al.
Am. J. Physiol. Cell Physiol. 2004;287:C633-C642.
ABSTRACT | FULL TEXT  

Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia
Manderscheid et al.
CVI 2004;11:742-751.
ABSTRACT | FULL TEXT  

In Vivo Interleukin-6 Protects Neutrophils from Apoptosis in Osteomyelitis
Asensi et al.
Infect. Immun. 2004;72:3823-3828.
ABSTRACT | FULL TEXT  

In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: Arterial in-line application in a porcine cardiac surgery model
Scholz et al.
J. Thorac. Cardiovasc. Surg. 2004;127:1735-1742.
ABSTRACT | FULL TEXT  

Inhibition of neutrophil activity in cardiac surgery with cardiopulmonary bypass: a novel strategy with the leukocyte inhibition module
Moreno et al.
Perfusion 2004;19:11-16.
ABSTRACT  

Suppression of mitochondria-dependent neutrophil apoptosis with thermal injury
Hu and Sayeed
Am. J. Physiol. Cell Physiol. 2004;286:C170-C178.
ABSTRACT | FULL TEXT  

Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone
Molloy et al.
Blood 2003;102:2653-2659.
ABSTRACT | FULL TEXT  

A role for PKC-delta and PI 3-kinase in TNF-alpha -mediated antiapoptotic signaling in the human neutrophil
Kilpatrick et al.
Am. J. Physiol. Cell Physiol. 2002;283:C48-C57.
ABSTRACT | FULL TEXT  

Deficiency in the Anti-Apoptotic Protein A1-a Results in a Diminished Acute Inflammatory Response
Orlofsky et al.
J. Immunol. 2002;168:1840-1846.
ABSTRACT | FULL TEXT  

Induction of Neutrophil Apoptosis by the Pseudomonas aeruginosa Exotoxin Pyocyanin: A Potential Mechanism of Persistent Infection
Usher et al.
J. Immunol. 2002;168:1861-1868.
ABSTRACT | FULL TEXT  

Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass
Chello et al.
Ann. Thorac. Surg. 2002;73:123-129.
ABSTRACT | FULL TEXT  

BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis
Moulding et al.
J. Leukoc. Biol. 2001;70:783-792.
ABSTRACT | FULL TEXT  

Apoptosis in sepsis: a new target for therapeutic exploration
OBERHOLZER et al.
FASEB J. 2001;15:879-892.
ABSTRACT | FULL TEXT  

Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis
O’Neill et al.
J. Leukoc. Biol. 2000;68:15-20.
ABSTRACT | FULL TEXT  

The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis
Leuenroth et al.
J. Leukoc. Biol. 2000;68:158-166.
ABSTRACT | FULL TEXT  

Decreased Apoptosis and Increased Activation of Alveolar Neutrophils in Bacterial Pneumonia
Droemann et al.
Chest 2000;117:1679-1684.
ABSTRACT | FULL TEXT  

Cytokine-Activated Endothelial Cells Delay Neutrophil Apoptosis in Vitro and in Vivo: A Role for Granulocyte/Macrophage Colony-Stimulating Factor
Coxon et al.
JEM 1999;190:923-934.
ABSTRACT | FULL TEXT  

Role of Granulocyte-Macrophage Colony-Stimulating Factor and Its Receptor in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis
Goodman et al.
Arch Surg 1999;134:1049-1054.
ABSTRACT | FULL TEXT  

Cytokines in myocardial injury: impact on cardiac surgical approach
Wan and Yim
Eur. J. Cardiothorac. Surg. 1999;16:S107-S111.
ABSTRACT | FULL TEXT  

The Murine Antiapoptotic Protein A1 Is Induced in Inflammatory Macrophages and Constitutively Expressed in Neutrophils
Orlofsky et al.
J. Immunol. 1999;163:412-419.
ABSTRACT | FULL TEXT  

Modulation of Endotoxin- and Enterotoxin-Induced Cytokine Release by In Vivo Treatment with beta -(1,6)-Branched beta -(1,3)-Glucan
Soltys and Quinn
Infect. Immun. 1999;67:244-252.
ABSTRACT | FULL TEXT  

The Influence of Human Endotoxemia on CD95-Induced Apoptosis
Lin et al.
Arch Surg 1998;133:1322-1327.
ABSTRACT | FULL TEXT  

Role of Interleukin 8 in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis
Goodman et al.
Arch Surg 1998;133:1234-1239.
ABSTRACT | FULL TEXT