The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils

Laggner, Maria; Acosta, Gabriela Sánchez; Kitzmüller, Claudia; Copic, Dragan; Грубер, Флориан; Altenburger, Lukas M.; Vorstandlechner, Vera; Gugerell, Alfred; Direder, Martin; Klas, Katharina; Bormann, Daniel; Peterbauer, Anja; Shibuya, Akira; Bohle, Barbara; Ankersmit, Hendrik Jan; Mildner, Michael

doi:10.1016/j.ebiom.2022.104093

Cited by 8 publications

(8 citation statements)

References 72 publications

(97 reference statements)

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“…The anti-inflammatory action of lipid extracts has already been investigated in different biological samples. For example, the lipid fraction of the secretome of γ-irradiated peripheral blood mononuclear cells lowered the inflammatory response of macrophages exposed to the inflammatory cues [41], and inhibited dendritic cell function 32403085, mast cell degranulation and basophil activation [42]. Elsewhere, pre-treatment of benzo pyrene-exposed rats with placental lipid extracts substantially attenuates the levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 [43].…”

Section: Discussionmentioning

confidence: 99%

“…Future lipidomic analyses of PRF will identify lipid candidates with strong anti-inflammatory activities that should be tested in our in vitro models. Examples of this approach are for instance, the secretome of γ-irradiated peripheral blood mononuclear cells exerts anti-inflammatory effects that are mainly attributed to the lipid fraction as shown for mast cells and basophils [42], dendritic cells [48], and macrophages [41] but also here, lipid species responsible for the observed effect remain unclear-even though extensively studied [42]. Another limitation is that we applied only one method of lipid extraction and we did not evaluate the efficiency of this method comparing to other methods available [49].…”

Section: Discussionmentioning

confidence: 99%

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Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages

Kargarpour

Panahipour

Mildner

et al. 2023

Cells

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Platelet-rich fibrin (PRF) has a potent anti-inflammatory activity but the components mediating this effect remain unknown. Blood lipids have anti-inflammatory properties. The question arises whether this is also true for the lipid fraction of PRF. To answer this question, lipid fractions of solid and liquid PRF were tested for their potential to lower the inflammatory response of ST2 bone marrow stromal cells and primary bone marrow macrophages exposed to IL1β and TNFα, and LPS, respectively. Cytokine production and the underlying signalling pathway were analysed by RT-PCR, immunoassays, and Western blotting. We report here that lipids from solid and liquid PRF substantially lowered cytokine-induced expression of IL6, CCL2 and CCL5 in ST2 cells. Moreover, the inflammatory response induced by Pam3CSK4, the agonist of Toll-like receptor (TLR) TLR2, was partially reduced by the lipid extracts in ST2 cells. The PRF lipids further reduced the LPS-induced expression of IL1β, IL6 and CCL5 in macrophages at the transcriptional level. This was confirmed by showing the ability of PRF lipids to diminish IL6 at the protein level in ST2 cells and macrophages. Likewise, PRF lipid extracts reduced the phosphorylation of p38 and JNK and moderately decreased the phosphorylation of NFκB-p65 in ST2 cells. These findings suggest that the lipid fraction is at least partially responsible for the anti-inflammatory activity of PRF in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages

Kargarpour

Panahipour

Mildner

et al. 2023

Cells

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“…Since we observed NETs inhibition at different steps of the NETs signalling pathway, we hypothesize that individual secretome fractions act on different signalling molecules. Recently, Laggner et al showed that lipids present in PBMCsec attenuate skin inflammation and allergic reactions by targeting dendritic cell function [ 34 ], as well as mast cell and basophil activation, respectively [ 56 ], suggesting that lipids are mainly responsible for the anti-inflammatory activities of PBMCsec. Several lipid species have been detected in PBMCsec, including phosphatidylserines, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatdiylethanolamines, and resolvins [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Paracrine Factors Released by Irradiated Peripheral Blood Mononuclear Cells on Neutrophil Extracellular Trap Formation

et al. 2022

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Neutrophil extracellular trap (NET)-formation represents an important defence mechanism for the rapid clearance of infections. However, exaggerated NET formation has been shown to negatively affect tissue-regeneration after injury. As our previous studies revealed the strong tissue-protective and regenerative properties of the secretome of stressed peripheral blood mononuclear cells (PBMCsec), we here investigated the influence of PBMCsec on the formation of NETs. The effect of PBMCsec on NET formation was assessed ex vivo in ionomycin stimulated neutrophils derived from healthy donors using flow cytometry, image stream analysis, and quantification of released extracellular DNA. The effect of PBMCsec on molecular mechanisms involved in NET formation, including Ca-flux, protein kinase C activity, reactive oxygen species production, and protein arginine deiminase 4 activity, were analysed. Our results showed that PBMCsec significantly inhibited NET formation. Investigation of the different biological substance classes found in PBMCsec revealed only a partial reduction in NET formation, suggesting a synergistic effect. Mechanistically, PBMCsec treatment did not interfere with calcium signalling and PKC-activation, but exerted anti-oxidant activity, as evidenced by reduced levels of reactive oxygen species and upregulation of heme oxygenase 1 and hypoxia inducible-factor 1 in PBMCsec-treated neutrophils. In addition, PBMCsec strongly inhibited the activation of protein arginine deiminase 4 (PAD4), ultimately leading to the inhibition of NET formation. As therapeutics antagonizing excessive NET formation are not currently available, our study provides a promising novel treatment option for a variety of conditions resulting from exaggerated NET formation.

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“…[65]. Фармакологические знания расширяются благодаря использованию современных научных методов, подтверждающих, что секретом мононуклеаров периферической крови изменяет сигнатуру транскриптома в сердце, печени и селезенке после экспериментального острого инфаркта миокарда [66], ослабляет активацию тучных клеток и базофилов [67], активирует проангиогенные и антипротеолитические процессы в клетках цельной крови и защищает эндотелиальный барьер [68], подавляет образование нейтрофильных внеклеточных ловушек [69], ослабляет гипертрофическое рубцевание кожи [70].…”

Section: лекции для врачейunclassified

Clinical Pharmacology Superlymph in Diseases of the Urogenital Tract Through the Prism of the Levels of Implementation of Its Effects

Yushkova,

Slabinskaya,

Yakovlev

2023

EPh

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The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils

Cited by 8 publications

References 72 publications

Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages

Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages

The Effect of Paracrine Factors Released by Irradiated Peripheral Blood Mononuclear Cells on Neutrophil Extracellular Trap Formation

Clinical Pharmacology Superlymph in Diseases of the Urogenital Tract Through the Prism of the Levels of Implementation of Its Effects

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