Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.

Abstract

INTRODUCTION:

Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations.

METHODS:

We studied this modification on CD14HIGH and CD14LOW monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process.

RESULTS:

HLA-DR on CD14HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14LOW cells only decreased after surgery, and to a lesser extent than on CD14HIGH monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14HIGH and CD14LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14HIGH versus CD14LOW monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone.

CONCLUSIONS:

This study reveals that HLA-DR expression is modulated differently on CD14HIGH (classical) versus CD14LOW (inflammatory) monocytes after systemic inflammation.

• Authors: Oh Yoen Kim, Antoine Monsel, Michèle Bertrand, Pierre Coriat, Jean-Marc Cavaillon, Minou Adib-Conquy
• Journal: Critical care (London, England) (Crit Care) Vol. 14 Issue 2 Pg. R61 ( 2010) ISSN: 1466-609X [Electronic] England
• PMID: 20385017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Antigens
• Lipopolysaccharide Receptors

Topics

• Aged
• Aorta, Abdominal (immunology, surgery)
• Carotid Arteries (immunology, surgery)
• Case-Control Studies
• Down-Regulation (immunology)
• Female
• Flow Cytometry
• Gene Expression (immunology)
• HLA-DR Antigens (biosynthesis, immunology)
• Humans
• Lipopolysaccharide Receptors (metabolism)
• Male
• Middle Aged
• Monocytes (cytology, immunology, metabolism)
• Polymerase Chain Reaction (methods)
• Systemic Inflammatory Response Syndrome (immunology, metabolism)