Different patterns of Siglec-9-mediated neutrophil death responses in septic shock

von Gunten, Stephan; Jakob, Stephan M; Geering, Barbara; Takala, Jukka; Simon, Hans-Uwe (2009). Different patterns of Siglec-9-mediated neutrophil death responses in septic shock. Shock, 32(4), pp. 386-92. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1097/SHK.0b013e3181a1bc98

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Sialic-acid-binding immunoglobulin-like lectin (Siglec) 9 mediates death signals in neutrophils. The objective of this study was to determine the heterogeneity of neutrophil death responses in septic shock patients and to analyze whether these ex vivo data are related to the severity and outcome of septic shock. In this prospective cohort study, blood samples of patients with septic shock (n = 26) in a medical-surgical intensive care unit (ICU) were taken within 24 h of starting the treatment of septic shock (phase A), after circulatory stabilization (phase B), and 10 days after admission or at ICU discharge if earlier (phase C). Neutrophil death was quantified in the presence and absence of an agonistic anti-Siglec-9 antibody after 24 h ex vivo. In phase A, two distinct patterns of Siglec-9-mediated neutrophil death were observed: resistance to neutrophil death (n = 14; Siglec-9 nonresponders) and increased neutrophil death (n = 12; Siglec-9 responders) after Siglec-9 ligation compared with neutrophils from normal donors. Experiments using a pharmacological pan-caspase-inhibitor provided evidence for caspase-independent neutrophil death in Siglec-9 responders upon Siglec-9 ligation. There were no differences between Siglec-9 responders and nonresponders in length of ICU or hospital stay of survivors or severity of organ dysfunction. Taken together, septic shock patients exhibit different ex vivo death responses of blood neutrophils after Siglec-9 ligation early in shock. Both the resistance and the increased susceptibility to Siglec-9-mediated neutrophil death tend to normalize within 72 h after shock. Further studies are required to understand the role of Siglec-9-mediated neutrophil death in septic shock.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Jakob, Stephan; Takala, Jukka and Simon, Hans-Uwe

ISSN:

1073-2322

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.1097/SHK.0b013e3181a1bc98

PubMed ID:

19295491

Web of Science ID:

000269928500007

URI:

https://boris.unibe.ch/id/eprint/30714 (FactScience: 194992)

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