Delay of neutrophil apoptosis in acute coronary syndromes.
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, FcgammaRIII). 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 alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta 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-gamma, GM-CSF, and IL-1beta 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.
Garlichs
C D
CD
Medicak Clinic II, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany. Christoph.Garlichs@rzmail.uni-erlangen.de
Eskafi
S
S
Cicha
I
I
Schmeisser
A
A
Walzog
B
B
Raaz
D
D
Stumpf
C
C
Yilmaz
A
A
Bremer
J
J
Ludwig
J
J
Daniel
W G
WG
D000208:Acute Disease; D000368:Aged; D000787:Angina Pectoris / Q000097:blood; D017209:Apoptosis; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D009504:Neutrophils / Q000473:pathology*; D015539:Platelet Activation
D016207:Cytokines