Mitochondria in monocytes and macrophages-implications for translational and basic research

Abstract

The mitochondrion plays a crucial role in the immune system particularly in regulating the responses of monocytes and macrophages to tissue injury, pathogens, and inflammation. In systemic diseases such as atherosclerosis and chronic kidney disease (CKD) it has been established that disruption to monocyte and macrophage function can lead to chronic inflammation. Polarization of macrophages into the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes results in distinct metabolic reprograming which corresponds to the progression and resolution of inflammation. In this review, we will discuss the role of the mitochondrion in monocyte and macrophage function and how these cells specifically influence the pathophysiology of atherosclerosis and CKD. We propose that assessing monocyte bioenergetics in different disease states could (1) enhance our understanding of the energetic perturbations occurring in systemic inflammatory conditions and (2) aid in identifying therapeutic interventions to mitigate these disorders in patients.

Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients

“…Interestingly, monocytes and macrophages exhibit a metabolic switch associated with the phenotypic switch to the pro-inflammatory M1 phenotype which is characterized by suppressed mitochondrial function [12,29]. To what extent these changes contribute to the modified bioenergetics in the monocytes isolated from PO-PCF is unclear and will require further investigation.…”

“…Recently, we have proposed that inflammatory cells, such as monocytes/macrophages, neutrophils or lymphocytes, can act as a biomarker of inflammation-associated mitochondrial dysfunction defined as changes in cellular bioenergetics [11][12][13]. Taken together, these findings suggested to us the hypothesis that the monocytes isolated from the PO-PCF, which is more pro-oxidant than the plasma, would exhibit increased mitochondrial dysfunction compared with cells isolated from the patients' blood.…”

“…On the basis of the glycolysis stress test, we found that approximately 72 % of the observed basal ECAR can be attributed to glycolysis ( Supplementary Figure S1). Monocytes can modulate their metabolic function on activation and become less oxidative and more glycolytic [12]. This can be visualized by plotting the basal OCR against the basal ECAR for each monocyte group using the data obtained in Figure 1.…”

The emerging theme of redox bioenergetics in health and disease

“…[24,25] The early association of cancer cells with an altered bioenergetics metabolism characterized by aerobic glycolysis has now been extended to encompass lymphocytes and monocytes as they adapt to their changing biological functions in normal physiology. [24,26,27] Early studies of mitochondrial function were largely based upon the disruption of tissues such as the heart or liver abundant in the organelle and characterization of the organelles isolated from their cellular milieu. The discovery of a sophisticated molecular postal system which directs proteins to different compartments within the mitochondrion resulted in the widespread notion that the mitochondrial proteome…”

The hydrogen molecule as antioxidant therapy: clinical application in hemodialysis and perspectives

“…High plasma MPO, released from injured neutrophils, is an independent risk factor for patient survival [96]. In chronic kidney disease, monocyte heterogeneity is widely acknowledged, and a growing body of circumstantial evidence suggests that intermediate monocytes (CD14(++)CD16(+)) is predisposed to secrete pro-inflammatory cytokines [97] and that polarization of monocyte and macrophage is disturbed, e.g., polarization of becoming dominant macrophages is impaired; enhanced pro-inflammatory (M1); and impaired anti-inflammatory (M2) phenotypes, which corresponds to the progression of inflammation [98,99].…”