Dendritic cells and their precursors isolated from human bronchoalveolar lavage: immunocytologic and functional properties.

Haarst, J. M. W. Van; Hoogsteden, H. C.; Wit, Harm J. de; Verhoeven, Gert T.; Havenith, Carin E.G.; Drexhage, Hemmo A.

doi:10.1165/ajrcmb.11.3.8086170

Cited by 75 publications

(68 citation statements)

References 10 publications

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“…Even if the critical role of DC in the initiation of immune response has been established (10), their involvement in Mtb infection is poorly defined. DC are highly represented in sites of Mtb infection at the onset of the inflammatory response (11)(12)(13). Immature DC present in the lung mucosa are specialized for Ag up-take and processing.…”

Section: Infection Of Human Macrophages and Dendritic Cells Withmentioning

confidence: 99%

Infection of Human Macrophages and Dendritic Cells withMycobacterium tuberculosisInduces a Differential Cytokine Gene Expression That Modulates T Cell Response

Giacomini¹,

Iona

Ferroni³

et al. 2001

The Journal of Immunology

387

340

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Macrophages and dendritic cells (DC) play an essential role in the initiation and maintenance of immune response to pathogens. To analyze early interactions between Mycobacterium tuberculosis (Mtb) and immune cells, human peripheral blood monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC) were infected with Mtb. Both cells were found to internalize the mycobacteria, resulting in the activation of MDM and maturation of MDDC as reflected by enhanced expression of several surface Ags. After Mtb infection, the proinflammatory cytokines TNF-α, IL-1, and IL-6 were secreted mainly by MDM. As regards the production of IFN-γ-inducing cytokines, IL-12 and IFN-α, was seen almost exclusively from infected MDDC, while IL-18 was secreted preferentially by macrophages. Moreover, Mtb-infected MDM also produce the immunosuppressive cytokine IL-10. Because IL-10 is a potent inhibitor of IL-12 synthesis from activated human mononuclear cells, we assessed the inhibitory potential of this cytokine using soluble IL-10R. Neutralization of IL-10 restored IL-12 secretion from Mtb-infected MDM. In line with these findings, supernatants from Mtb-infected MDDC induced IFN-γ production by T cells and enhanced IL-18R expression, whereas supernatants from MDM failed to do that. Neutralization of IFN-α, IL-12, and IL-18 activity in Mtb-infected MDDC supernatants by specific Abs suggested that IL-12 and, to a lesser extent, IFN-α and IL-18 play a significant role in enhancing IFN-γ synthesis by T cells. During Mtb infection, macrophages and DC may have different roles: macrophages secrete proinflammatory cytokines and induce granulomatous inflammatory response, whereas DC are primarily involved in inducing antimycobacterial T cell immune response.

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Section: Infection Of Human Macrophages and Dendritic Cells Withmentioning

confidence: 99%

Infection of Human Macrophages and Dendritic Cells withMycobacterium tuberculosisInduces a Differential Cytokine Gene Expression That Modulates T Cell Response

Giacomini¹,

Iona

Ferroni³

et al. 2001

The Journal of Immunology

387

340

View full text Add to dashboard Cite

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“…In rats, Havenith et al (13) showed that bronchoalveolar lavage cells (BALs) could be divided into a high-autofluorescent (AF) fraction containing almost exclusively Mphs (as assessed by mor-phology and cytochemical features), and a low-AF fraction containing monocytes, DCs, lymphocytes, and granulocytes. When extrapolated to human BAL samples, this strategy yielded analogous results, with the low-AF BAL fraction containing cells with morphological, immunofluorescent, and functional features of DCs, while high-AF BAL cells were virtually all Mphs with extremely poor APC function or even immunosuppressive activity (14). In the mouse, a similar method has been lacking.…”

mentioning

confidence: 92%

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

2004

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BackgroundThe need to accurately discriminate dendritic cells (DCs) and macrophages (Mphs) in mouse lungs is critical given important biological differences. However, a validated flow cytometry–based method is still lacking, resulting in much confusion between both cell types.MethodsSingle‐cell suspensions freshly obtained from collagenase‐digested lung tissue were stained with a CD11c‐specific monoclonal antibody, detected using a PE‐Cy5 or APC‐conjugated secondary reagent. Cellular immunophenotype was simultaneously explored using a panel of PE‐conjugated markers. The FL1 or FITC‐detection channel was reserved for the assessment of autofluorescence.ResultsCD11c‐bright cells were heterogeneous and displayed a bimodal distribution with regard to autofluorescence (AF). CD11c+/low‐AF cells were lineage‐negative and showed features compatible with myeloid DCs. This was confirmed by morphology, potent T‐cell stimulatory function in a mixed‐leukocyte reaction, surface expression of MHCII and costimulatory molecules, and further immunophenotypical criteria, including the expression of Mac‐1 and absence of CD8α. In contrast, CD11c+/high‐AF cells displayed the features of pulmonary Mphs, including typical Mph morphology, very weak induction of T‐cell proliferation, low to absent expression of MHCII and costimulatory molecules, and very low levels of Mac‐1 as well as F4/80. We also show that only CD11c+/high‐AF cells strongly expressed the macrophage marker MOMA‐2, while interestingly Mac‐3 was expressed at high levels by CD11c+/high‐AF and low‐AF alike.ConclusionsThis study shows that the combination of CD11c‐expression and autofluorescence is necessary and sufficient to accurately separate DCs from macrophage subpopulations in mouse lungs. © 2004 Wiley‐Liss, Inc.

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“…On identification and internalization of pathogens, DCs move to the draining lymph nodes of the lung to instigate specific cellular and humoral immune responses. Extensive network of bone marrow-derived DCs exist in the mucosa of the nose and the large conducting airways, the alveolar lumen, and the connective tissue surrounding the blood vessels and the pleura (Holt et al, , 1994Schon-Hegrad et al, 1991;van Haarst et al, 1994;Lambrecht et al, 1998;Gonzalez-Juarrero and Orme, 2001;von Garnier and Nicod, 2009). The migration of the airway DCs in response to an immunogenic stimulus is rapid (e.g.…”

Section: Dendritic Cells (Dcs)mentioning

confidence: 99%

Cellular Defences of the Lung: Comparative Perspectives

Maina¹

2012

Respiratory Diseases

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'Our lungs are highly complex organs that are exquisitely specialized for gas exchange and host defense.' Rawlins (2010) 1. Introduction General considerationsThe most important function of the lung is to acquire molecular oxygen and eliminate carbon dioxide. Except probably for the gastrointestinal system, no other organ in the body interacts with the external environment as constantly and as intimately as the respiratory system. For example, during a 24 hour period, at rest, the human lung is ventilated ~25,000 times with ~20,000 L of air (e.g. Burri, 1985; Brain, 1996), it has a respiratory surface area (RSA) of ~140 m 2 (about the size of a tennis court) which is located in the acini that lie no more than 40 to 50 cm from the external environment (air) (e.g. Weibel, 1984), and the thickness of the blood-gas (tissue) barrier (BGB) (harmonic mean thickness, ht) is 0.62 μm, a value about one-fiftieth of the thickness of a foolscap paper or that of a human head hair (Gehr et al., 1978(Gehr et al., , 1990a. By weight, each day, more than 20 kg of air enters and leaves the human body, a load that far exceeds that of food and water ingested during the same time period (Brain, 1996). Depending on the level of air pollution, different types and quantities of foreign particulates and microbial pathogens are inhaled. While large RSA and thin BGB increase gas exchange, the concomitant downside to these structural properties is that they make the lung a leading portal of entry and therefore attack by pathogenic micro-organisms, damage by allergens and particulates, and injury by noxious gases (e.g. Brain, , 1992Lambrecht et al. 2001;Garn et al., 2006). The inhaled particulates are deposited on the epithelial lining of the conducting airways and that of the peripheral air spaces where they are retained for various durations before they are removed or destroyed (e.g. Geiser et al., 1988; Gehr et al., 1990 a, b). Brain (1996) observed that 'the lung is unique in that the marriage between environment and lung disease is profound. The respiratory system threfore forms a huge challenge to the body's immune integrity (e.g. von Garnier and Nicod, 2009 , 1993;Schwartz, 1994;Brunekreef et al., 1995;Ware, 2000;Pope, 2000;Nemmar et al., 2002;Pope et al., 2002;Suwa et al., 2002;Schulz et al., 2005;Kaufman, 2010;Brook et al., 2010; van den Hooven et al., 2011;Kampfrath et al., 2011 gc.ca/ccdpc-cpcmc/crdmrc/facts_gen_e.html). According to the Canadian Lung Association (CLA), the economic burden of respiratory disease in the Country is ~3 billion ($US) dollars (http://www.bukisa.com/articles/455926_lung-health-occupational-healthincidence#ixzz1I4jwMvBX). Based on net changes in gross domestic product (GDP) growth forecasts, the estimated annual cost of SARS (Sudden Avian Respiratory Syndrome) in Asia exceeds 10 billion dollars ($US) (Lee and McKibbin, 2003;Fan, 2003;McKibbin and Sidorenko, 2006) and according to the World Bank's estimates, an influenza pandemic may result in a loss (expenditure) of 800 billion dollars ($US) (Brahm...

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Dendritic cells and their precursors isolated from human bronchoalveolar lavage: immunocytologic and functional properties.

Cited by 75 publications

References 10 publications

Infection of Human Macrophages and Dendritic Cells withMycobacterium tuberculosisInduces a Differential Cytokine Gene Expression That Modulates T Cell Response

Infection of Human Macrophages and Dendritic Cells withMycobacterium tuberculosisInduces a Differential Cytokine Gene Expression That Modulates T Cell Response

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

Cellular Defences of the Lung: Comparative Perspectives

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