Function-Associated Surface Molecules on Airway Dendritic Cells in Cigarette Smokers

Bratke, Kai; Klug, Michael G.; Bier, August; Julius, Peter; Kuepper, Michael; Virchow, J. Christian; Lommatzsch, Marek

doi:10.1165/rcmb.2007-0400oc

Cited by 62 publications

(68 citation statements)

References 25 publications

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“…Accordingly, human immature and maturing DCs have been shown to exert neutrophilic chemotactic activity in vitro upon stimulation with cigarette smoke extract (29). Still, it is unclear why the inflammatory DC influx to the lung, which in several reports has been shown to involve CCR2 (30), CCR5 (31), and/or CCR6 (21), should be so strongly CCR7-dependent. The presence of CCR7 on DCs in the lung (Fig.…”

Section: Discussionmentioning

confidence: 99%

CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice

Demoor

Bracke

Vermaelen

et al. 2009

The Journal of Immunology

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Peribronchial lymphoid follicles have recently been identified as one of the hallmark features of (severe) chronic obstructive pulmonary disease (COPD). However, little is known about the relative contribution of peribronchial lymphoid follicles vs mediastinal lymph nodes in inflammatory responses in COPD patients and animal models. In a murine model of COPD, we studied inflammatory responses in airways, lungs, and mediastinal lymph nodes of wild-type (WT) vs CCR7 knockout (CCR7−/−) mice upon subacute or chronic exposure to cigarette smoke (CS). Although crucial for the organization of the secondary lymphoid organs, CCR7 was not required for the development of chronic CS-induced pulmonary lymphoid follicles. Moreover, T cell numbers were significantly increased in airways and lungs of air-exposed CCR7−/− mice, and they continued to increase upon chronic CS exposure. Unexpectedly, subacute CS-induced inflammation in airways and lungs, including airway neutrophilia and the recruitment of inflammatory-type CD11b+ dendritic cells, depended greatly on CCR7. In the draining lymph nodes, chronic CS exposure induced CCR7-dependent recruitment of airway-derived dendritic cells, accompanied by increases in CD4+ and CD8+ T cells. Correspondingly, CS exposure up-regulated mRNA expression of CCR7 ligands CCL19 and CCL21-Ser in lymph nodes of WT mice, but not CCR7−/− mice. In the lungs of WT mice, chronic CS exposure significantly increased CCL19 mRNA and protein. Furthermore, double staining for CCL19 and pro-surfactant protein C showed that alveolar type II cells express high levels of CCL19. These data unveil a so far unappreciated role for CCR7 in modulating inflammatory responses in airways and lungs.

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Section: Discussionmentioning

confidence: 99%

CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice

Demoor

Bracke

Vermaelen

et al. 2009

The Journal of Immunology

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“…Moreover, there is an increase in the total number of T-lymphocytes in lung parenchyma and peripheral and central airways of COPD patients, which is more prominent for CD8+ cells [19,51]. These patients show an increase in mature dendritic cells (DCs) in the peripheral airways, and DCs from smokers display an increased expression of CD80 and CD86 [52]; it is likely that material in the lungs of smokers is taken up by these cells and presented by DC major histocompatibility complex class I molecules to CD8+ lymphocytes. Once activated by antigen-bearing DCs, T-cells may access the lung parenchyma by means of their tissue-specific chemokine receptors [20].…”

Section: Effect Of Cigarette Smoke Exposure On the Human Respiratory mentioning

confidence: 99%

Impact of cigarette smoke exposure on host-bacterial pathogen interactions

Garmendia¹,

Morey²,

Bengoechea³

2011

European Respiratory Journal

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The human respiratory tract of individuals with normal lung function maintains a finetuned balance, being asymptomatically colonised by the normal microbiota in the upper airways and sterile in the lower tract. This equilibrium may be disrupted by the exposure to insults such as cigarette smoke. In the respiratory tract, the complex and noxious nature of inhaled cigarette smoke alters host-microorganism interaction dynamics at all anatomical levels, causing infections in many cases. Moreover, continuous exposure to cigarette smoke itself causes deleterious effects on the host that can trigger the development of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. COPD is an irreversible airflow obstruction associated with emphysema, fibrosis, mucus hypersecretion and persistent colonisation of the lower airways by opportunistic pathogens. COPD patients keep a stable (without exacerbation) but progressively worsening condition and suffer periodic exacerbations caused, in most cases, by infections. Although smoking and smoking-associated diseases are associated with a high risk of infection, most therapies aim to reduce inflammatory parameters, but do not necessarily take into account the presence of persistent colonisers. The effect of cigarette smoke on host-pathogen interaction dynamics in the respiratory tract, together with current and novel therapies, is discussed.

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“…Chronic cigarette smokers display a characteristic increase in the number of Langerhans' cells, a subtype of myeloid DCs (mDCs), in the airways [13][14][15]. Even more Langerhans' cells are found in the airways of smokers with COPD [6] or PLCH [3,16].…”

mentioning

confidence: 99%

“…However, the significance of the Langerhans' cell phenotype in the pathogenesis of these diseases remains unknown. Using a recently described flow cytometric method for analysing DCs in human bronchoalveolar lavage fluid (BALF) [17,18], the expression of functionassociated surface molecules on airway mDCs were characterised in chronic cigarette smokers [15]. The airway mDCs of smokers display increased expression of the co-stimulatory molecules CD80 and CD86, but reduced expression of the lymph node homing receptor, CC chemokine receptor (CCR) 7 [15].…”

mentioning

confidence: 99%

“…Using a recently described flow cytometric method for analysing DCs in human bronchoalveolar lavage fluid (BALF) [17,18], the expression of functionassociated surface molecules on airway mDCs were characterised in chronic cigarette smokers [15]. The airway mDCs of smokers display increased expression of the co-stimulatory molecules CD80 and CD86, but reduced expression of the lymph node homing receptor, CC chemokine receptor (CCR) 7 [15]. These findings led to the hypothesis that mDCs of smokers might show increased ability to induce T-cell responses, but reduced ability to migrate to draining lymph nodes [15].…”

mentioning

confidence: 99%

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Acute effects of tobacco smoke on human airway dendritic cells in vivo

Lommatzsch¹,

Bratke²,

Knappe³

et al. 2009

European Respiratory Journal

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Airway dendritic cells (DCs) play a key role in smoke-related lung diseases; however, the acute effects of tobacco smoke on human airway DCs in vivo are unknown.A total of 16 smokers underwent bronchoalveolar lavage at two time-points: directly after a 4-h period of nonsmoking (no smoke exposure); and directly after a 4-h period during which eight cigarettes were smoked (acute smoke exposure). Using flow cytometry, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), as well as function-associated surface molecules on mDCs, were analysed in bronchoalveolar lavage fluid (BALF) and in blood.The numbers of macrophages, lymphocytes, neutrophils, eosinophils and pDCs were unchanged in BALF following acute smoke exposure, as compared to no smoke exposure. In contrast, there was a strong increase in mDC number in BALF and a concomitant decrease in mDC number in blood following acute smoke exposure. In addition, acute smoke exposure led to an increase in the expression of the surface molecules blood dendritic cell antigen 1 and 4 and a decrease in the expression of the lung homing receptor, CC chemokine receptor 5, on mDCs in BALF.Acute tobacco smoke inhalation results in an immediate and selective recruitment of mDCs into human airways, which might reflect the very early reaction of the adaptive immune system to smoke exposure.

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Function-Associated Surface Molecules on Airway Dendritic Cells in Cigarette Smokers

Cited by 62 publications

References 25 publications

CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice

CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice

Impact of cigarette smoke exposure on host-bacterial pathogen interactions

Acute effects of tobacco smoke on human airway dendritic cells in vivo

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