Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

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

Abstract

ABSTRACT: INTRODUCTION: Decreased expression of 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 rarely 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 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, MARCH-1 mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on day one 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.