Characterization of CB2 Receptor Expression in Peripheral Blood Monocytes of Acute Ischemic Stroke Patients

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

doi:10.1007/s12975-020-00851-8

Cited by 15 publications

(15 citation statements)

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“…Some factors were documented as influencing CB 2 receptor expression in human leukocytes. CB 2 expression can increase during inflammation as it is the case in eosinophils from symptomatic allergic donors compared to healthy controls ( Frei et al, 2016 ; Larose et al, 2017 ), in monocytes of patients after ischemic stroke ( Greco et al, 2021 ), in myeloid and plasmacytoid dendritic cells of patients with multiple sclerosis ( Chiurchiu et al, 2013 ; Sanchez Lopez et al, 2015 ) and in T lymphocytes of Non-Hodgkin’s lymphomas ( Rayman et al, 2007 ; Robinson et al, 2013 ). On the other hand, LPS decreased CB 2 receptor expression in isolated dendritic cells and B lymphocytes ( Lee et al, 2001 ; Do et al, 2004 ).…”

Section: Factors Influencing Cb 2 Receptor Express...mentioning

confidence: 99%

Expression and Functions of the CB2 Receptor in Human Leukocytes

et al. 2022

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The cannabinoid CB2 receptor was cloned from the promyeloid cell line HL-60 and is notably expressed in most, if not all leukocyte types. This relatively restricted localization, combined to the absence of psychotropic effects following its activation, make it an attractive drug target for inflammatory and autoimmune diseases. Therefore, there has been an increasing interest in the past decades to identify precisely which immune cells express the CB2 receptor and what are the consequences of such activation. Herein, we provide new data on the expression of both CB1 and CB2 receptors by human blood leukocytes and discuss the impact of CB2 receptor activation in human leukocytes. While the expression of the CB2 mRNA can be detected in eosinophils, neutrophils, monocytes, B and T lymphocytes, this receptor is most abundant in human eosinophils and B lymphocytes. We also review the evidence obtained from primary human leukocytes and immortalized cell lines regarding the regulation of their functions by the CB2 receptor, which underscore the urgent need to deepen our understanding of the CB2 receptor as an immunoregulator in humans.

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Section: Factors Influencing Cb 2 Receptor Express...mentioning

confidence: 99%

Expression and Functions of the CB2 Receptor in Human Leukocytes

et al. 2022

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“…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. By contrast, the percentage of CD14++/CD16-events (corresponding to classical monocyte subtype) was not affected [19]. Interestingly, we also found that the increase in CB2 protein expression in CD16+ monocytes positively correlated with stroke severity, likely representing a compensatory response to limit damage if considering their anti-inflammatory and pro-angiogenic functions [20,21].…”

Section: Introductionmentioning

confidence: 59%

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

Greco¹,

Demartini²,

Zanaboni

et al. 2021

IJMS

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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.

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“…Similarly, LPS preconditioning reduced neutrophil composition in the blood after transient MCAo compared with non-preconditioned control mice, which was suggested to contribute to reduced infiltration in the ischemic brain (97) Besides neutrophils, circulating monocytes are recruited by monocyte chemoattractant protein (MCP)-1 and extensively infiltrate into the ischemic parenchyma, reaching a peak 2-3 days after the insult (90,98). A higher monocyte blood count has been associated with ischemic stroke severity and adverse prognosis of patients (99)(100)(101)(102). This is coherent with the elevated number of Ly-6C+ monocytes that we observed in the blood of mice subjected to transient MCAo, an effect that is attenuated by pre-exposure to the neuroprotective PC stimulus.…”

Section: Discussionmentioning

confidence: 99%

Ischemic Preconditioning Modulates the Peripheral Innate Immune System to Promote Anti-Inflammatory and Protective Responses in Mice Subjected to Focal Cerebral Ischemia

et al. 2022

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The development of tolerance triggered by a sublethal ischemic episode (preconditioning, PC) involves a complex crosstalk between neurons, astrocytes and microglia, although the role of the peripheral immune system in this context is largely unexplored. Here, we report that severe cerebral ischemia caused by transient middle cerebral artery occlusion (MCAo) in adult male mice elevates blood counts of inflammatory neutrophils and monocytes, and plasma levels of miRNA-329-5p. These inflammatory responses are prevented by ischemic PC induced by 15 min MCAo, 72h before the severe insult (1h MCAo). As compared with sham-operated animals, mice subjected to either ischemic PC, MCAo or a combination of both (PC+MCAo) display spleen contraction. However, protein levels of Ym1 (a marker of polarization of myeloid cells towards M2/N2 protective phenotypes) are elevated only in spleen from the experimental groups PC and PC+MCAo, but not MCAo. Conversely, Ym1 protein levels only increase in circulating leukocytes from mice subjected to 1h MCAo, but not in preconditioned animals, which is coincident with a dramatic elevation of Ym1 expression in the ipsilateral cortex. By immunofluorescence analysis, we observe that expression of Ym1 occurs in amoeboid-shaped myeloid cells, mainly representing inflammatory monocytes/macrophages and neutrophils. As a result of its immune-regulatory functions, ischemic PC prevents elevation of mRNA levels of the pro-inflammatory cytokine interleukin (IL)-1β in the ipsilateral cortex, while not affecting IL-10 mRNA increase induced by MCAo. Overall, the elevated anti-inflammatory/pro-inflammatory ratio observed in the brain of mice pre-exposed to PC is associated with reduced brain infarct volume and ischemic edema, and with amelioration of functional outcome. These findings reaffirm the crucial and dualistic role of the innate immune system in ischemic stroke pathobiology, extending these concepts to the context of ischemic tolerance and underscoring their relevance for the identification of novel therapeutic targets for effective stroke treatment.

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Characterization of CB2 Receptor Expression in Peripheral Blood Monocytes of Acute Ischemic Stroke Patients

Cited by 15 publications

References 65 publications

Expression and Functions of the CB2 Receptor in Human Leukocytes

Expression and Functions of the CB2 Receptor in Human Leukocytes

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

Ischemic Preconditioning Modulates the Peripheral Innate Immune System to Promote Anti-Inflammatory and Protective Responses in Mice Subjected to Focal Cerebral Ischemia

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