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Downstream effects of endocannabinoid on blood cells: implications for health and disease

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Abstract

Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are the most biologically active members, are polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome proliferator-activated receptors. Depending on the target engaged, these bioactive mediators can regulate different signalling pathways, at both central and peripheral levels. The biological action of eCBs is tightly controlled by a plethora of metabolic enzymes which, together with the molecular targets of these substances, form the so-called “endocannabinoid system”. The ability of eCBs to control manifold peripheral functions has received a great deal of attention, especially in the light of their widespread distribution in the body. In particular, eCBs are important regulators in blood, where they modulate haematopoiesis, platelet aggregation and apoptosis, as well as chemokine release and migration of immunocompetent cells. Here, we shall review the current knowledge on the pathophysiological roles of eCBs in blood. We shall also discuss the involvement of eCBs in those disorders affecting the haematological system, including cancer and inflammation. Knowledge gained to date underlines a fundamental role of the eCB system in blood, thus suggesting that it may represent a therapeutic promise for a broad range of diseases involving impaired hematopoietic cell functions.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

Met-AEA:

2-methylarachidonyl-(2′-fluoroethyl)amide

ABHD:

a/b-hydrolase

AML:

Acute myeloid leukaemia

ApoE:

Apolipoprotein E

CB:

Cannabinoid

CM:

Chronic migraine

eCB:

Endocannabinoid

EMT:

eCB membrane transporter

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-related kinase

FAAH:

Fatty acid amide hydrolase

fMLP:

Formyl-Met-Leu-Phe

G-CSF:

Granulocyte-colony-stimulating factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HETE-G:

Hydroxyeicosatetraenoyl glycerylester

(S)-HAEA:

Hydroxyeicosatetraenoylethanolamide

IBD:

Inflammatory bowel disease

IFNγ:

Interferon γ

IL:

Interleukin

LTB4:

Leukotriene B4

LPS:

Lipopolysaccharide

MCP-1:

Macrophage-chemotactic protein 1

MMP-9:

Matrix metalloprotease-9

MOH:

Medication-overuse headache

MAGL:

Monoacylglyceride lipase

MS:

Multiple sclerosis

NAPE-PLD:

N-acylphosphatydiletanolamine phospholipase D

anandamide, AEA:

N-arachidonoylethanolamine

NK:

Natural killer

NO:

Nitric oxide

PEA:

N-palmitoylethanolamine

OEA:

N-oleoylethanolamine

PPARs:

Peroxisome proliferator-activated receptors

PI3 K:

Phosphoinositide 3kinase

PGE2 :

Prostaglandin E2

Th:

T helper

TRPV1:

Transient receptor potential vanilloid 1

TNFα:

Tumour necrosis factor α

CB1 :

Type-1 cannabinoid receptor

CB2 :

Type-2 cannabinoid receptor

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Acknowledgments

We wish to thank all colleagues who have contributed over the years to our studies on endocannabinoids in blood cell biology. Financial support from Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2009 to L.A., PRIN 2010–2011 to M.M.), and by Fondazione TERCAS (Grant 2009–2012 to M.M.).

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Authors and Affiliations

  1. Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133, Rome, Italy

    Valeria Gasperi, Daniela Evangelista, Isabella Savini, Luciana Avigliano & Maria Valeria Catani

  2. San Raffaele Institute Sulmona, L’Aquila, Italy

    Domenico Del Principe

  3. Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy

    Mauro Maccarrone

  4. European Center for Brain Research (CERC)/Santa Lucia Foundation, Rome, Italy

    Mauro Maccarrone

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  1. Valeria Gasperi
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  2. Daniela Evangelista
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  3. Isabella Savini
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  4. Domenico Del Principe
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  5. Luciana Avigliano
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  6. Mauro Maccarrone
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  7. Maria Valeria Catani
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Correspondence to Maria Valeria Catani.

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M. Maccarrone and M. V. Catani are equal senior authors.

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Gasperi, V., Evangelista, D., Savini, I. et al. Downstream effects of endocannabinoid on blood cells: implications for health and disease. Cell. Mol. Life Sci. 72, 3235–3252 (2015). https://doi.org/10.1007/s00018-015-1924-0

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  • DOI: https://doi.org/10.1007/s00018-015-1924-0

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