Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla

Macrophage activation, first generalized to the M1/M2 dichotomy, is a complex and central process of the innate immune response. Simply, M1 describes the classical proinflammatory activation, leading to tissue damage, and M2 the alternative activation promoting tissue repair. Given the central role...

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Main Authors: Kai Qiao, Lydia M. Le Page, Myriam M. Chaumeil
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/11/7/410
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author Kai Qiao
Lydia M. Le Page
Myriam M. Chaumeil
author_facet Kai Qiao
Lydia M. Le Page
Myriam M. Chaumeil
author_sort Kai Qiao
collection DOAJ
description Macrophage activation, first generalized to the M1/M2 dichotomy, is a complex and central process of the innate immune response. Simply, M1 describes the classical proinflammatory activation, leading to tissue damage, and M2 the alternative activation promoting tissue repair. Given the central role of macrophages in multiple diseases, the ability to noninvasively differentiate between M1 and M2 activation states would be highly valuable for monitoring disease progression and therapeutic responses. Since M1/M2 activation patterns are associated with differential metabolic reprogramming, we hypothesized that hyperpolarized <sup>13</sup>C magnetic resonance spectroscopy (HP <sup>13</sup>C MRS), an innovative metabolic imaging approach, could distinguish between macrophage activation states noninvasively. The metabolic conversions of HP [1-<sup>13</sup>C]pyruvate to HP [1-<sup>13</sup>C]lactate, and HP [1-<sup>13</sup>C]dehydroascorbic acid to HP [1-<sup>13</sup>C]ascorbic acid were monitored in live M1 and M2 activated J774a.1 macrophages noninvasively by HP <sup>13</sup>C MRS on a 1.47 Tesla NMR system. Our results show that both metabolic conversions were significantly increased in M1 macrophages compared to M2 and nonactivated cells. Biochemical assays and high resolution <sup>1</sup>H MRS were also performed to investigate the underlying changes in enzymatic activities and metabolite levels linked to M1/M2 activation. Altogether, our results demonstrate the potential of HP <sup>13</sup>C MRS for monitoring macrophage activation states noninvasively.
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spelling doaj.art-53c78a2652dd4099848c693ea050c0842023-11-22T01:10:04ZengMDPI AGMetabolites2218-19892021-06-0111741010.3390/metabo11070410Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 TeslaKai Qiao0Lydia M. Le Page1Myriam M. Chaumeil2Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USADepartment of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USADepartment of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USAMacrophage activation, first generalized to the M1/M2 dichotomy, is a complex and central process of the innate immune response. Simply, M1 describes the classical proinflammatory activation, leading to tissue damage, and M2 the alternative activation promoting tissue repair. Given the central role of macrophages in multiple diseases, the ability to noninvasively differentiate between M1 and M2 activation states would be highly valuable for monitoring disease progression and therapeutic responses. Since M1/M2 activation patterns are associated with differential metabolic reprogramming, we hypothesized that hyperpolarized <sup>13</sup>C magnetic resonance spectroscopy (HP <sup>13</sup>C MRS), an innovative metabolic imaging approach, could distinguish between macrophage activation states noninvasively. The metabolic conversions of HP [1-<sup>13</sup>C]pyruvate to HP [1-<sup>13</sup>C]lactate, and HP [1-<sup>13</sup>C]dehydroascorbic acid to HP [1-<sup>13</sup>C]ascorbic acid were monitored in live M1 and M2 activated J774a.1 macrophages noninvasively by HP <sup>13</sup>C MRS on a 1.47 Tesla NMR system. Our results show that both metabolic conversions were significantly increased in M1 macrophages compared to M2 and nonactivated cells. Biochemical assays and high resolution <sup>1</sup>H MRS were also performed to investigate the underlying changes in enzymatic activities and metabolite levels linked to M1/M2 activation. Altogether, our results demonstrate the potential of HP <sup>13</sup>C MRS for monitoring macrophage activation states noninvasively.https://www.mdpi.com/2218-1989/11/7/410Hyperpolarized <sup>13</sup>CMR spectroscopymetabolismmacrophage activationinflammationinnate immune response
spellingShingle Kai Qiao
Lydia M. Le Page
Myriam M. Chaumeil
Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
Metabolites
Hyperpolarized <sup>13</sup>C
MR spectroscopy
metabolism
macrophage activation
inflammation
innate immune response
title Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
title_full Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
title_fullStr Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
title_full_unstemmed Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
title_short Non-Invasive Differentiation of M1 and M2 Activation in Macrophages Using Hyperpolarized <sup>13</sup>C MRS of Pyruvate and DHA at 1.47 Tesla
title_sort non invasive differentiation of m1 and m2 activation in macrophages using hyperpolarized sup 13 sup c mrs of pyruvate and dha at 1 47 tesla
topic Hyperpolarized <sup>13</sup>C
MR spectroscopy
metabolism
macrophage activation
inflammation
innate immune response
url https://www.mdpi.com/2218-1989/11/7/410
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