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Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets.

ABSTRACT: Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.

SUBMITTER: Loret T

PROVIDER: S-EPMC9008410 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets.

Loret Thomas T de Luna Luis Augusto Visani LAV Fordham Alexander A Arshad Atta A Barr Katharine K Lozano Neus N Kostarelos Kostas K Bussy Cyrill C

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220215 11

Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO ...[more]

PMID: 35166457

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Project description:Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies. Infiltration of lymphocytes is observed in autoimmune epilepsies, especially the classical paraneoplastic encephalitides with antibodies against intracellular tumor antigens. The presence of lymphocytes in the CNS also has been found in focal cerebral dysplasia type 2 and in cortical tubers. Various autoantibodies have been shown to be associated with temporal lobe epilepsy (TLE) and hippocampal sclerosis of unknown etiology, which may be due to the presence of viral DNA. During the last decade, an increasing number of antineuronal autoantibodies directed against membranous epitopes have been discovered and are associated with various neurologic syndromes, including limbic encephalitis. A major challenge in epilepsy is to define biomarkers, which would allow the recognition of patient populations who might benefit from immune-modulatory therapies. Some peripheral inflammatory markers appear to be differentially expressed in patients with medically controlled and medically refractory and, as such, could be used for diagnostic, prognostic, or therapeutic purposes. Establishing an autoimmune basis in patients with drug-resistant epilepsy allows for efficacious and targeted immunotherapy. Although current immunotherapies can give great benefit to the correctly identified patient, there are limitations to their efficacy and they may have considerable side effects. Thus the identification of new immunomodulatory compounds remains of utmost importance.

Dataset Information

Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets.

Publications

Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets.

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