Monocytes and Macrophages

Nares, Salvador; Wahl, Sharon M.

doi:10.1016/b978-012455900-4/50287-7

Cited by 3 publications

(8 citation statements)

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“…Six independent cultures were obtained from 6 independent donors. Monocytes were isolated using CD14 MicroBeads (Miltenyi Biotec, Auburn, CA, USA) according to manufacturer's instructions and cultured as previously described [ 12 , 20 , 21 ]. Briefly, isolated monocytes were plated onto duplicate 12-well tissue culture-treated plates (BD Biosciences, San Jose, CA, USA) at a density of 5 × 10 5 cells/cm 2 in serum-free DMEM with L-glutamine (Cellgro, Manassas, VA, USA) containing 50 μg/mL gentamicin (Sigma, St. Louis, MO, USA) at 37 C, 5% CO 2 to promote monocyte attachment.…”

Section: Methodsmentioning

confidence: 99%

“…These long-lived, multifaceted cells, strategically poised along portals of entry, perform numerous functions of vital importance to the host. In addition to their key role in immunity [ 12 ], the macrophage is recognized as the major mediator of normal connective tissue turnover and maintenance, as well as for orchestrating repair during wound healing [ 13 - 18 ]. It has a dualistic role to receive, amplify, and transmit signals to fibroblasts, endothelial cells, and vascular smooth muscle cells by producing pro-inflammatory and catabolic cytokines.…”

Section: Introductionmentioning

confidence: 99%

“…It has a dualistic role to receive, amplify, and transmit signals to fibroblasts, endothelial cells, and vascular smooth muscle cells by producing pro-inflammatory and catabolic cytokines. However, during tissue turnover and wound healing it secretes anabolic peptide growth factors [ 12 ]. Given this duality of function, any perturbation can lead to pathological processes.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

et al. 2010

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BackgroundPhenytoin (PHT) has been reported to induce gingival (gum) overgrowth (GO) in approximately 50% of patients taking this medication. While most studies have focused on the effects of PHT on the fibroblast in the pathophysiology underlying GO, few studies have investigated the potential regulatory role of macrophages in extracellular matrix (ECM) turnover and secretion of proinflammatory mediators. The aim of this study was to evaluate the effects of PHT and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin (HPPH) on LPS-elicited MMP, TIMP, TNF-α and IL-6 levels in macrophages.MethodsHuman primary monocyte-derived macrophages (n = 6 independent donors) were pretreated with 15-50 μg/mL PHT-Na+ or 15-50 μg/mL HPPH for 1 hour. Cells were then challenged with 100 ng/ml purified LPS from the periodontal pathogen, Aggregatibacter actinomycetemcomitans. Supernatants were collected after 24 hours and levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, TIMP-2, TIMP-3, TIMP-4, TNF-α and IL-6 determined by multiplex analysis or enzyme-linked immunoadsorbent assay.ResultsA dose-dependent inhibition of MMP-1, MMP-3, MMP-9, TIMP-1 but not MMP-2 was noted in culture supernatants pretreated with PHT or HPPH prior to LPS challenge. MMP-12, TIMP-2, TIMP-3 and TIMP-2 were not detected in culture supernatants. High concentrations of PHT but not HPPH, blunted LPS-induced TNF-α production although neither significantly affected IL-6 levels.ConclusionThe ability of macrophages to mediate turnover of ECM via the production of metalloproteinases is compromised not only by PHT, but its metabolite, HPPH in a dose-dependent fashion. Further, the preferential dysregulation of macrophage-derived TNF-α but not IL-6 in response to bacterial challenge may provide an inflammatory environment facilitating collagen accumulation without the counteracting production of MMPs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

et al. 2010

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“…20 On PAMP recognition, initiation of innate responses through generation of an arsenal of genes that encode effector proteins ensues to contain and/or clear the inciting agent, with a striking reprogramming of the complex molecular and cellular networks within and between immune cells. As coordinators, these cells orchestrate the transition to and the propagation of the adaptive arm of the immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Monocytes were purified from the mononuclear cell layer using centrifugal elutriation 18 and divided into three groups for immature monocytes and generation of macrophages and DCs as described 19,20 in three independent experiments with cells from three donors. Freshly isolated monocytes were used immediately after elutriation, whereas donor-matched macrophage and DC studies were initiated after confirmation of differentiation on day 7.…”

Section: Myeloid Cell Preparation and Stimulationmentioning

confidence: 99%

Rapid Myeloid Cell Transcriptional and Proteomic Responses to Periodontopathogenic Porphyromonas gingivalis

Nares

Moutsopoulos

Angelov

et al. 2009

The American Journal of Pathology

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Long-lived monocytes, macrophages, and dendritic cells (DCs) are Toll-like receptor-expressing, antigenpresenting cells derived from a common myeloid lineage that play key roles in innate and adaptive immune responses. Based on immunohistochemical and molecular analyses of inflamed tissues from patients with chronic destructive periodontal disease, these cells, found in the inflammatory infiltrate, may drive the progressive periodontal pathogenesis. To investigate early transcriptional signatures and subsequent proteomic responses to the periodontal pathogen, Porphyromonas gingivalis, donor-matched human blood monocytes, differentiated DCs, and macrophages were exposed to P. gingivalis lipopolysaccharide (LPS) and gene expression levels were measured by oligonucleotide microarrays. In addition to striking differences in constitutive transcriptional profiles between these myeloid populations, we identify a P. gingivalis LPS-inducible convergent, transcriptional core response of more than 400 annotated genes/ESTs among these populations, reflected by a shared, but quantitatively distinct, proteomic response. Nonetheless, clear differences emerged between the monocytes, DCs, and macrophages. The finding that long-lived myeloid inflammatory cells, particularly DCs, rapidly and aggressively respond to P. gingivalis LPS by generating chemokines, proteases, and cytokines capable of driving T-helper cell lineage polarization without evidence of corresponding immunosuppressive pathways highlights their prominent role in host defense and progressive tissue pathogenesis. The shared, unique, and/or complementary transcriptional and proteomic profiles may frame the context of the host response to P. gingivalis, contributing to the destructive nature of periodontal inflammation.

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Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects

Lee

Nguyen

Doan

et al. 2023

Viruses

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The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

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Monocytes and Macrophages

Cited by 3 publications

References 73 publications

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

Rapid Myeloid Cell Transcriptional and Proteomic Responses to Periodontopathogenic Porphyromonas gingivalis

Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects

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