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

• Published in: Critical care (London, England) Vol. 14; no. 2; p. R61
• Main Authors: Kim, Oh Yoen, Monsel, Antoine, Bertrand, Michèle, Coriat, Pierre, Cavaillon, Jean-Marc, Adib-Conquy, Minou
• Format: Journal Article
• Language: English
• Published: London BioMed Central 13.04.2010; BioMed Central Ltd; National Library of Medicine - MEDLINE Abstracts
• Subjects: Aged; Aorta, Abdominal - immunology; Aorta, Abdominal - surgery; Carotid Arteries - immunology; Carotid Arteries - surgery; Case-Control Studies; Critical Care Medicine; Development and progression; Down-Regulation - immunology; Emergency Medicine; Female; Flow Cytometry; Gene expression; Gene Expression - immunology; Genetic aspects; Genetic regulation; HLA class II antigens; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - immunology; Humans; Inflammation; Intensive; Lipopolysaccharide Receptors - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Monocytes; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Observations; Physiological aspects; Polymerase Chain Reaction - methods; Properties; Systemic Inflammatory Response Syndrome - immunology; Systemic Inflammatory Response Syndrome - metabolism; France; CD14LOW Cell; Systemic Inflammatory Response Syndrome; Monocyte Subset; CD14HIGH Cell; Human Leukocyte Antigen Class
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1466-609X
• DOI: 10.1186/cc8959

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 CD14 HIGH and CD14 LOW 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 CD14 HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14 LOW cells only decreased after surgery, and to a lesser extent than on CD14 HIGH 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 CD14 HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14 HIGH and CD14 LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14 HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14 HIGH versus CD14 LOW 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 CD14 HIGH ( classical ) versus CD14 LOW ( inflammatory ) monocytes after systemic inflammation.