Sladek Z, Rysanek D: CD14 expression, apoptosis and necrosis in resident and inflammatory macrophages from virgin bovine mammary gland

Sládek, Z.; Rysanek, D.

doi:10.17221/7777-vetmed

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…The main role of CD14 is to induce bacterial phagocytosis, although it is also involved in the clearance of apoptotic cells. Additionally, CD14 has been attributed to a role in the induction of survival of cells that express it [ 38 ]. Induction of its expression in anti-inflammatory M2 Mphs and mDCs co-cultured with ASCs may imply an ASC-mediated increased cell survival and resistance to cell death.…”

Section: Discussionmentioning

confidence: 99%

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2

Ortiz-Virumbrales¹,

Menta²,

Pérez³

et al. 2020

Stem Cell Res Ther

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Background Mesenchymal stem cells (MSCs) activate the endogenous immune regulatory system, inducing a therapeutic effect in recipients. MSCs have demonstrated the ability to modulate the differentiation of myeloid cells toward a phagocytic and anti-inflammatory profile. Allogeneic, adipose-derived MSCs (ASCs) have been investigated for the management of complex perianal fistula, with darvadstrocel being the first ASC therapy approved in Europe in March 2018. Additionally, ASCs are being explored as a potential treatment in other indications. Yet, despite these clinical advances, their mechanism of action is only partially understood. Methods Freshly isolated human monocytes from the peripheral blood were differentiated in vitro toward M0 non-polarized macrophages (Mphs), M1 pro-inflammatory Mphs, M2 anti-inflammatory Mphs, or mature dendritic cells (mDCs) in the presence or absence of ASCs, in non-contact conditions. The phenotype and function of the differentiated myeloid populations were determined by flow cytometry, and their secretome was analyzed by OLINK technology. We also investigated the capacity of ASCs to modulate the phenotype and function of terminally differentiated M1 Mphs. The role of soluble factors interleukin (IL)-6 and prostaglandin E2 (PGE2) on the ability of ASCs to modulate myeloid cells was assessed using neutralization assays, CRISPR/Cas9 knock-down of cyclooxygenase 2 (COX-2), and ASC-conditioned medium assays using pro-inflammatory stimulus. Results Co-culture of monocytes in the presence of ASCs resulted in the polarization of Mphs and mDCs toward an anti-inflammatory and phagocytic phenotype. This was characterized by an increase in phagocytic receptors on the cell surface of Mphs (M0, M1, and M2) and mDCs, as well as modulation of chemokine receptors and reduced expression of pro-inflammatory, co-stimulatory molecules. ASCs also modulated the secretome of Mphs and mDCs, demonstrated by reduced expression of pro-inflammatory factors and increased expression of anti-inflammatory and reparative factors. Chemical inhibition of PGE2 with indomethacin abolished this modulatory effect, whereas treatment with a neutralizing anti-IL-6 antibody resulted in a partial abolishment. The knock-down of COX-2 in ASCs and the use of IL-1β-activated ASC-conditioned media confirmed the key role of PGE2 in ASC-mediated myeloid modulation. In our in vitro experimental settings, ASCs failed to modulate the phenotype and function of terminally polarized M1 Mphs. Conclusions The results demonstrate that ASCs are able to modulate the in vitro differentiation of myeloid cells toward an anti-inflammatory and reparative profile. This modulatory effect was mediated mainly by PGE2 and, to a lesser extent, IL-6.

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Section: Discussionmentioning

confidence: 99%

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2

Ortiz-Virumbrales¹,

Menta²,

Pérez³

et al. 2020

Stem Cell Res Ther

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“…Leukocyte size and granule content can be assessed by forward and side scatter measurements on flow cytometry, respectively. Hence, lymphocytes are identified as small cells containing small granules, while monocyte/macrophages are identified as larger cells with granules [28][29][30][31] . On flow cytometry, splenic lymphocytes were separated into region R1 and splenic myeloid cells including monocyte/macrophages and neutrophils into region R2.…”

Section: Discussionmentioning

confidence: 99%

89Zr anti-CD44 immuno-PET monitors CD44 expression on splenic myeloid cells and HT29 colon cancer cells

Park

Jung

Lee

et al. 2021

Sci Rep

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CD44 is a cell-surface glycoprotein involved in cell–cell interaction, adhesion, and migration. CD44 is found on colon cancer cells and on immune cells. Previous studies of 89Zr PET imaging of CD44 have relied on an anti-human antibody (Ab), which can influence biodistribution in murine models. In this study, we used an Ab that cross-reacts with both human and mouse origin CD44 of all isoforms to unveil the type of leukocyte responsible for high splenic anti-CD44 uptake and investigate how its regulation can influence tumor immuno-PET. The Ab was site-specifically labeled with 89Zr-deferoxamine on cysteine residues. 89Zr-anti-CD44 demonstrated high-specific binding to HT29 human colon cancer cells and monocytic cells that showed CD44 expression. When 89Zr-anti-CD44 was administered to Balb/C nude mice, there was remarkably high splenic uptake but low SNU-C5 tumor uptake (1.2 ± 0.7%ID/g). Among cells isolated from Balb/C mouse spleen, there was greater CD44 expression on CD11b positive myeloid cells than lymphocytes. In cultured monocytic and macrophage cells, LPS stimulation upregulated CD44 expression and increased 89Zr-anti-CD44 binding. Similarly, normal Balb/C mice that underwent lipopolysaccharide (LPS) stimulation showed a significant upregulation of CD44 expression on splenic myeloid cells. Furthermore, LPS treatment stimulated a 2.44-fold increase of 89Zr-anti-CD44 accumulation in the spleen, which was attributable to splenic myeloid cells. Finally, in Balb/C nude mice bearing HT29 tumors, we injected 89Zr-anti-CD44 with greater Ab doses to reduce binding to splenic cells. The results showed lower spleen uptake and improved tumor uptake (2.9 ± 1.3%ID/g) with a total of 300 μg of Ab dose, and further reduction of spleen uptake and greater tumor uptake (5.7 ± 0.0%ID/g) with 700 μg Ab dose. Thus, using an 89Zr labeled Ab that cross-reacts with both human and mouse CD44, we demonstrate that CD44 immuno-PET has the capacity to monitor CD44 regulation on splenic myeloid cells and may also be useful for imaging colon tumors.

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“…24 In LPS-induced inflammation, it is highly expressed on the inflammatory macrophages as compared to naïve or anti-inflammatory macrophages. 25 It is a key molecule involved in the recruitment of macrophages to the LPSinduced inflammatory site. 26 As shown in Fig.…”

Section: Peroxidase Mimicking Activity Of Hapb Nanoparticlesmentioning

confidence: 99%

Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages

et al. 2022

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Sladek Z, Rysanek D: CD14 expression, apoptosis and necrosis in resident and inflammatory macrophages from virgin bovine mammary gland

Cited by 8 publications

References 42 publications

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2

89Zr anti-CD44 immuno-PET monitors CD44 expression on splenic myeloid cells and HT29 colon cancer cells

Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages

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