Macrophages in bronchoalveolar lavage fluid are not representative of macrophages in granulomas of the lungs of BCG‐infected mice

Nibbering, Peter H.; Heide, G. A. van de; Furth, R. van

doi:10.1002/path.1711570313

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…However, our studies suggest that the recruitment of neutrophils into the lungs of infected pregnant mice may be site specific. This mirrors the finding that cytokine expression or cellular recruit- on April 30, 2020 by guest http://jvi.asm.org/ ment into the BAL fluid is not always an absolute representation of the immune responses occurring throughout the lung (11,58,59). Neutrophils were not elevated in the bronchial tubes (BAL fluid) but rather the alveolar spaces and interstitium of pregnant animals.…”

Section: Discussionsupporting

confidence: 66%

Fatal Outcome of Pandemic H1N1 2009 Influenza Virus Infection Is Associated with Immunopathology and Impaired Lung Repair, Not Enhanced Viral Burden, in Pregnant Mice

Marcelin¹,

Aldridge²,

Duan³

et al. 2011

J Virol

101

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In most cases, the pandemic H1N1 2009 influenza virus (pH1N1) strain is self-limiting and mirrors infection by commonly circulating seasonal influenza virus strains. However, pregnant and postpartum women are at greater risk for severe clinical manifestations (20,44,47,73). In one study, the Centers for Disease Control and Prevention reported a death rate of 20% in pregnant women in the United States who were hospitalized with pH1N1-related symptoms (72). Among these deaths, 64% occurred within the third trimester of pregnancy. Serious influenza-induced complications in pregnant women are not a new phenomenon. In sharp contrast to the general population, pregnant women had disproportionately high rates of hospital admission and mortality during the previous influenza pandemics: the

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Section: Discussionsupporting

confidence: 66%

Fatal Outcome of Pandemic H1N1 2009 Influenza Virus Infection Is Associated with Immunopathology and Impaired Lung Repair, Not Enhanced Viral Burden, in Pregnant Mice

Marcelin¹,

Aldridge²,

Duan³

et al. 2011

J Virol

101

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“…In contrast, in our cohort, no decrease in CXCR3 + CD4 + T cells was observed in the lung parenchyma, and IPF patients actually exhibited increased CXCR3 + CD4 + T cells in the LLN compared to controls. As IPF is an interstitial disease, the BAL studies may not be representative of the underlying process within the lung parenchyma, and therefore, the subsets of leukocytes obtained from BAL may be very different compared to tissue-resident subsets (53, 54). …”

Section: Discussionmentioning

confidence: 99%

Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function

et al. 2016

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RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. While it has been suggested that T cells may contribute to IPF pathogenesis, these studies have focused primarily on T cells outside of the pulmonary interstitium. Thus, the role of T cells in the diseased lung tissue remains unclear.ObjectiveTo identify whether specific CD4+ T cell subsets are differentially represented in lung tissue from patients with IPF.MethodsCD4+ T cell subsets were measured in lung tissue obtained from patients with IPF at the time of lung transplantation, and from age- and gender-matched organ donors with no known lung disease. Subsets were identified by their surface expression of CCR4, CCR6, and CXCR3 chemokine receptors. CD4+ T cell subsets were correlated with measurements of lung function obtained prior to transplantation.ResultsCompared to controls, IPF patients had a higher proportion of lung CD4+ T cells, a higher proportion of CCR4+ CD4+ T cells, and a lower proportion of CCR6+ CD4+ T cells. The increase in CCR4+ CD4+ T cells in IPF lung tissue was not due to increased Tregs. Intriguingly, the increase in the ratio of CCR4+ cells to CCR6+ cells correlated significantly with better lung function.ConclusionOur findings suggest a new paradigm that not all T cell infiltrates in IPF lungs are detrimental, but instead, specialized subsets may actually be protective. Thus, augmentation of the chemokines that recruit protective T cells, while blocking chemokines that recruit detrimental T cells, may constitute a novel approach to IPF therapy.

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“…Furthermore, macrophages from different tissues and even within the same tissue can show considerable phenotypic heterogeneity [33]. Additionally, it is unclear to what extent primary AMs isolated from BAL fluid are representative of the AM population resident within the alveoli [34]. Further studies will be required to better understand what impact the different protocols used to establish macrophage surrogates may have on the resulting gene expression profiles and perhaps better understand how the resulting surrogates reflect the many primary macrophage phenotypes observed within physiological and pathophysiological settings.…”

Section: Discussionmentioning

confidence: 99%

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

et al. 2012

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BackgroundAlveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60) are frequently used to model macrophage function.MethodsThe availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR) and ion channel expression in alveolar macrophages and their widely used surrogates.ResultsThe complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates.ConclusionsThe data described in this report provides insight into the appropriate choice of cell models for investigating macrophage biology and highlights the importance of confirming experimental data in primary alveolar macrophages.

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Macrophages in bronchoalveolar lavage fluid are not representative of macrophages in granulomas of the lungs of BCG‐infected mice

Cited by 6 publications

References 21 publications

Fatal Outcome of Pandemic H1N1 2009 Influenza Virus Infection Is Associated with Immunopathology and Impaired Lung Repair, Not Enhanced Viral Burden, in Pregnant Mice

Fatal Outcome of Pandemic H1N1 2009 Influenza Virus Infection Is Associated with Immunopathology and Impaired Lung Repair, Not Enhanced Viral Burden, in Pregnant Mice

Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

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