CD163 as a Potential Biomarker of Monocyte Activation in Ischemic Stroke Patients.

Rosaria Greco,Cristina Tassorelli,Diana Amantea,Alessandra Persico,Anna Maria Zanaboni,Chiara Demartini,Andrea Morotti,Elisa Candeloro,Elena Tumelero

doi:10.3390/ijms22136712

Abstract

In ischemic stroke patients, a higher monocyte count is associated with disease severity and worse prognosis. The complex correlation between subset phenotypes and functions underscores the importance of clarifying the role of monocyte subpopulations. We examined the subtype-specific distribution of the CD163+ and CD80+ circulating monocytes and evaluated their association with the inflammatory status in 26 ischemic stroke patients and 16 healthy controls. An increased percentage of CD163+/CD16+ and CD163+/CD14++ events occurred 24 and 48 h after a stroke compared to the controls. CD163+ expression was more pronounced in CD16+ non-classical and intermediate monocytes, as compared to CD14+ classical subtype, 24 h after stroke. Conversely, the percentage of CD80+/CD16+ events was unaffected in patients; meanwhile, the percentage of CD80+/CD14+ events significantly increased only 24 h after stroke. Interleukin (IL)-1beta, TNF-alpha, and IL-4 mRNA levels were higher, while IL-10 mRNA levels were reduced in total monocytes from patients versus controls, at either 24 h or 48 h after stroke. The percentage of CD163+/CD16+ events 24 h after stroke was positively associated with NIHSS score and mRS at admission, suggesting that stroke severity and disability are relevant triggers for CD163+ expression in circulating CD16+ monocytes.

Highlights

The pathobiology of an ischemic stroke is influenced by the activation of immune responses occurring both locally in the brain and in the peripheral circulation
In a recent clinical study, we reported a significant elevation of the percentage of CD14++/CD16+ intermediate and CD14+/CD16+ non-classical monocyte subsets, as well as their relative expression of the cannabinoid receptor-2 (CB2), 24 and 48 h after stroke
The percentage of CD80+/CD16+ events was unaffected after stroke (Figure 2a), whereas the percentage of CD80+/CD14++ events was significantly

Summary

Introduction

The pathobiology of an ischemic stroke is influenced by the activation of immune responses occurring both locally in the brain and in the peripheral circulation. Evidence from animal models and patients highlights that ischemic insult results in rapid activation of local microglia, followed by stimulation and cerebral recruitment of circulating monocytes that differentiate into macrophages or dendritic cells, influencing the progression of ischemic damage [1,2,3,4]. Monocytes modulate the immune response by polarizing toward diverse phenotypes that display tangled, often paradoxical, and still poorly characterized functions. Several studies suggest that the disease stage and some risk factors can differentially affect specific monocyte subsets; these cells may be a biomarker predictive of outcomes. The few studies performed to date have revealed that the more abundant (CD14+) classical monocyte subset triggers detrimental effects; on the contrary, the less-represented (CD16+) populations may exert beneficial functions [14,15]

Methods

Results

Discussion

Conclusion