Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.
BACKGROUND
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.
Kim
Oh Yoen
OY
Unit Cytokines & Inflammation, Institut Pasteur, 28 rue Dr, Roux, Paris, France. ohkite@hotmail.com
Monsel
Antoine
A
Bertrand
Michèle
M
Coriat
Pierre
P
Cavaillon
Jean-Marc
JM
Adib-Conquy
Minou
M
D000368:Aged; D001012:Aorta, Abdominal / Q000276:immunology / Q000601:surgery; D002339:Carotid Arteries / Q000276:immunology / Q000601:surgery; D016022:Case-Control Studies; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000378:metabolism*
D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors
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