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Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Friman)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2002 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 6, no 4, 363-370 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin.

MATERIALS AND METHODS: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques.

RESULTS: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.001), despite complement activation, while the monocyte CD88 expression was unchanged. The receptor reduction correlated significantly to the APACHE II score (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow.

DISCUSSION: In contrast to the findings in animals, it is concluded that granulocyte CD88 expression is reduced at the time when the diagnosis of severe sepsis or septic shock can clinically be made. The reason for this needs further investigation but it may be due to a previous complement activation or to cytokine effects.

Place, publisher, year, edition, pages
2002. Vol. 6, no 4, 363-370 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-93166PubMedID: 12225614OAI: oai:DiVA.org:uu-93166DiVA: diva2:166560
Available from: 2005-05-12 Created: 2005-05-12 Last updated: 2010-11-29Bibliographically approved
In thesis
1. C5a Receptor Expression in Severe Sepsis and Septic Shock
Open this publication in new window or tab >>C5a Receptor Expression in Severe Sepsis and Septic Shock
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In patients with sepsis, the activation of the cascade systems, for example the complement system with the generation of C5a, is followed by a state of immunosuppression with impaired bactericidal capacity caused by suppression of the neutrophil granulocytes. To inhibit the C5a-induced systemic inflammatory and the following anti-inflammatory responses, different anti-C5a strategies have been successful in experimental models of sepsis. In animals and in healthy volunteers after injection of lipopolysaccharide (LPS), an up-regulation of the C5a receptor (C5aR) has been reported. Before designing clinical studies, it was of importance to increase the knowledge of C5a and C5aR regulation in humans.

At the time when the diagnosis of severe sepsis or septic shock can be established clinically, granulocyte C5aR expression, analysed by flow cytometer, was shown to be reduced, whereas monocyte C5aR expression was unchanged. There was a correlation between granulocyte C5aR expression and the severity of disease, as measured by the APACHE II score.

Ex vivo incubation of whole blood with LPS resulted in a reduction in granulocyte C5aR expression. Such a reduction was not found in isolated cells, indicating that the effect was mediated via plasma factors, such as C5a, IL-8 and TNF-α which all were shown to reduce C5aR expression ex vivo.

Although there was a trend between chemotaxis, as measured by migration in a modified Boyden chamber, and C5aR expression on granulocytes from patients with severe sepsis or septic shock or from healthy individuals, the correlation failed to reach statistical significance.

It is concluded that granulocyte C5aR expression is affected by several plasma factors and that a reduction is clinically evident at the time of the sepsis diagnosis. Reduced granulocyte C5aR expression is associated with an impaired chemotaxis but does not alone limit the chemotactic response.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 48
Keyword
Communicable diseases, C5a receptor, granulocyte, severe sepsis, septic shock, chemotaxis, anti-C5a treatment, ex vivo incubation, C5a, interleukin-8, LPS, Infektionssjukdomar
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-5832 (URN)91-554-6275-8 (ISBN)
Public defence
2005-06-02, Enghoffsalen, ing 50, bv, Akademiska sjukhuset, Uppsala, 09:15
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Supervisors
Available from: 2005-05-12 Created: 2005-05-12Bibliographically approved

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Furebring, MiaVenge, PerNilsson, BoSjölin, Jan

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