Proteomic and bioinformatics profile of paired human alveolar macrophages and peripheral blood monocytes

Tomechko, Sara E.; Lundberg, Kathleen C.; Jarvela, Jessica; Bebek, Gürkan; Chesnokov, Nicole G.; Schlatzer, Daniela; Ewing, Rob M.; Boom, W. Henry; Chance, Mark R.; Silver, Richard F.

doi:10.1002/pmic.201400496

Cited by 16 publications

(13 citation statements)

References 36 publications

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“…A direct comparison between AMs in lung microenvironment and PBMCs was not the scope of our study, but we rather aimed to characterize the inflammasome activity in the two distinct compartments (tumour lung environment and the periphery). Peripheral–Blood monocytes and macrophages have well established differences in TLR signaling and immune cell trafficking with AMs exist in both healthy [ 63 , 64 ] and COPD patients [ 65 , 66 ], which comes in agreement with our findings. Another limitation of our study is that, only TLR4 stimulation by LPS was used and a global TLR impairment in the LC AMs cannot be excluded, as already reported in COPD AMs[ 37 ] [ 38 ].…”

Section: Discussionsupporting

confidence: 92%

NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer

et al. 2018

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Lung cancer (LC) remains the leading cause of cancer-related mortality. The interaction of cancer cells with their microenvironment, results in tumor escape or elimination. Alveolar macrophages (AMs) play a significant role in lung immunoregulation, however their role in LC has been outshined by the study of tumor associated macrophages. Inflammasomes are key components of innate immune responses and can exert either tumor-suppressive or oncogenic functions, while their role in lung cancer is largely unknown. We thus investigated the NLRP3 pathway in Bronchoalveolar Lavage derived alveolar macrophages and peripheral blood leukocytes from patients with primary lung cancer and healthy individuals. IL-1β and IL-18 secretion was significantly higher in unstimulated peripheral blood leukocytes from LC patients, while IL-1β secretion could be further increased upon NLRP3 stimulation. In contrast, in LC AMs, we observed a different profile of IL-1β secretion, characterized mainly by the impairment of IL-1β production in NLRP3 stimulated cells. AMs also exhibited an impaired TLR4/LPS pathway as shown by the reduced induction of IL-6 and TNF-α. Our results support the hypothesis of tumour induced immunosuppression in the lung microenvironment and may provide novel targets for cancer immunotherapy.

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Section: Discussionsupporting

confidence: 92%

NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer

et al. 2018

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“…Although antiretroviral therapy suppresses viral replication in lymphoid tissue and has achieved considerable success at combating HIV viral infection, it is becoming evident that clinically latent reservoirs of HIV persist in individuals on antiretroviral therapy 4 5 8 43 . Retroviral persistence has been reported in brain cells including microglia, astrocytes, mononuclear cells, dendritic cells, CD4 lymphocytes, perivascular and tissue macrophages 5 44 45 .…”

Section: Discussionmentioning

confidence: 99%

HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1

Yuan

Fan

Staitieh

et al. 2017

Sci Rep

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Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy. Here, we investigated the potential role of TREM-1 in HIV latency in macrophages. Our data show that human macrophages infected with HIV show an increased expression of TREM-1. In parallel, direct exposure to the HIV-related proteins Tat or gp120 induces TREM-1 expression in macrophages and confers anti-apoptotic attributes.NF-κB p65 silencing identified that these proteins induce TREM-1 in p65-dependent manner. TREM-1 silencing in macrophages exposed to HIV-related proteins led to increased caspase 3 activation and reduced Bcl-2 expression, rendering them susceptible to apotosis. These novel data reveal that TREM-1 may play a critical role in establishing HIV reservoir in macrophages by inhibiting apoptosis. Therefore, targeting TREM-1 could be a novel therapeutic approach to enhance clearance of the HIV reservoir, at least within the macrophage pools.

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“…A total of 15 µg of protein from each sample was digested with LysC for 1 hr and trypsin overnight at 37°C. Reverse phase LC‐MS/MS was performed as described (Tomechko et al, ), except that 600 ng of peptide digests was loaded on the HPLC column and the gradient of solvent B ranged from 2% to 40% over 210 min.…”

Section: Methodsmentioning

confidence: 99%

A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings

Seabra

Szoko

Erdin

et al. 2017

American J of Med Genetics Pt A

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Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78–98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject’s lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1,014 were significantly up- or down-regulated compared to controls (q<0.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down-regulation of: (1) intracellular components involved in organization of membranes, organelles and vesicles; (2) aspects of cell cycle control, signal transduction and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities.

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Proteomic and bioinformatics profile of paired human alveolar macrophages and peripheral blood monocytes

Cited by 16 publications

References 36 publications

NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer

NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer

HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1

A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings

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