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Stimulation of Fas signaling down-regulates activity of neutrophils from major trauma patients with SIRS.
- Source :
-
Immunobiology [Immunobiology] 2011 Mar; Vol. 216 (3), pp. 334-42. Date of Electronic Publication: 2010 Aug 19. - Publication Year :
- 2011
-
Abstract
- Posttrauma apoptosis resistance of neutrophils (PMN) is related to overshooting immune responses, systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Recently, we have shown that the apoptosis resistance in circulating PMN from severely injured patients which is known to be mediated by high serum levels of pro-inflammatory cytokines can be overcome by the activation of Fas death receptor. Here, we aimed to study whether stimulation of surface Fas leads to the inactivation of hyperactivated PMN from critically ill patients with SIRS. PMN from 23 multiple trauma patients (mean injury severity score (ISS) 34±1.9) were isolated at day 1 after admission to the trauma center. PMN from 17 volunteer blood donors served as controls. Neutrophil activity has been determined after ex vivo short (1 h) and long-term (4 h) stimulation of freshly isolated PMN with immobilized agonistic anti-Fas antibodies. We found neutrophil chemotactic migration in response to IL-8, phagocytosis and oxidative burst to be significantly inhibited in control cells already after short-term (1 h) Fas stimulation. In contrast, inactivation of trauma PMN by agonistic anti-Fas antibodies was found to be efficient only after long-term (4 h) incubation of cells with agonistic antibodies. Thus, in trauma PMN down-regulation of neutrophil activity seems to be delayed when compared to cells isolated from healthy controls, suggesting impaired susceptibility for Fas stimulation in these cells. Interestingly, whereas Fas-mediated inhibition of phagocytosis and oxidative burst could be prevented by the broad range caspase inhibitor t-butoxycarbonyl-aspartyl(O-methyl)-fluoromethyl ketone (BocD-fmk), the chemotactic activity in response to IL-8 was unaffected. In conclusion, we demonstrate that stimulation of neutrophil Fas does not only initiate apoptosis but also induces inhibition of neutrophil functions, partially by non-apoptotic signaling.<br /> (Copyright © 2010 Elsevier GmbH. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Apoptosis
Chemotaxis, Leukocyte
Fas Ligand Protein metabolism
Female
Flow Cytometry
Humans
Interleukin-8 immunology
Male
Middle Aged
Multiple Organ Failure
Phagocytosis
Respiratory Burst
Signal Transduction
Systemic Inflammatory Response Syndrome complications
Wounds and Injuries complications
Wounds and Injuries metabolism
Neutrophils immunology
Neutrophils metabolism
Systemic Inflammatory Response Syndrome immunology
Systemic Inflammatory Response Syndrome metabolism
Wounds and Injuries immunology
fas Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3279
- Volume :
- 216
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 20832139
- Full Text :
- https://doi.org/10.1016/j.imbio.2010.07.005