Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo, Robert; Kroening, Paula R.; Parambil, Joseph G.; Kita, Hirohito

doi:10.1016/j.molimm.2008.04.014

Cited by 97 publications

(83 citation statements)

References 43 publications

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“…PGE2 is a key prostanoid produced in the lung in response to a variety of insults, from LPS to tobacco smoke (35,36). Although it exhibits direct barrier-enhancing effects on pulmonary endothelium (32), PGE2 also displays barrier-disruptive effects, particularly in epithelial cells (37), degrading occludin protein in pulmonary epithelium (38) and potentiating the development of pulmonary edema (39).…”

Section: Discussionmentioning

confidence: 99%

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Robertson

Sauer

Gold

et al. 2012

Am J Respir Cell Mol Biol

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Mechanical ventilation is necessary for patients with acute respiratory failure, but can cause or propagate lung injury. We previously identified cyclooxygenase-2 as a candidate gene in mechanical ventilationinduced lung injury. Our objective was to determine the role of cyclooxygenase-2 in mechanical ventilation-induced lung injury and the effects of cyclooxygenase-2 inhibition on lung inflammation and barrier disruption. Mice were mechanically ventilated at low and high tidal volumes, in the presence or absence of pharmacologic cyclooxygenase-2-specific inhibition with 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404). Lung injury was assessed using markers of alveolar-capillary leakage and lung inflammation. Cyclooxygenase-2 expression and activity were measured by Western blotting, real-time PCR, and lung/plasma prostanoid analysis, and tissue sections were analyzed for cyclooxygenase-2 staining by immunohistochemistry. High tidal volume ventilation induced lung injury, significantly increasing both lung leakage and lung inflammation relative to control and low tidal volume ventilation. High tidal volume mechanical ventilation significantly induced cyclooxygenase-2 expression and activity, both in the lungs and systemically, compared with control mice and low tidal volume mice. The immunohistochemical analysis of lung sections localized cyclooxygenase-2 expression to monocytes and macrophages in the alveoli. The pharmacologic inhibition of cyclooxygenase-2 with CAY10404 significantly decreased cyclooxygenase activity and attenuated lung injury in mice ventilated at high tidal volume, attenuating barrier disruption, tissue inflammation, and inflammatory cell signaling. This study demonstrates the induction of cyclooxygenase-2 by mechanical ventilation, and suggests that the therapeutic inhibition of cyclooxygenase-2 may attenuate ventilator-induced acute lung injury. Keywords: cyclooxygenase-2; mechanical ventilation; lung injuryMechanical ventilation is a life-saving therapy for patients with acute respiratory failure. However, it can cause or worsen lung injury, particularly at larger tidal volumes (1, 2). Positive-pressure mechanical ventilation may expose the lungs, and particularly the alveoli, to overdistention, resulting in volutrauma with the subsequent release of inflammatory and vasoactive cytokines and prostanoids that propagate lung injury (1, 3). Therapeutic trials aimed at decreasing lung injury have focused on minimizing the damage from mechanical ventilation with the use of "protective" low tidal volume ventilator strategies. However, because of the heterogeneity of lung injury, even at lower tidal volumes, different regions of the lung may be subjected to higher stretch (4). Although using lower tidal volumes decreases markers of injury and inflammation and significantly improves survival in patients with acute lung injury, mortality remains high (1). A better understanding of the mechanisms by which mechanical ventilation injures the lungs will be key in identifying ...

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Section: Discussionmentioning

confidence: 99%

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Robertson

Sauer

Gold

et al. 2012

Am J Respir Cell Mol Biol

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“…27), previously identified as potent producers of CXCL1 (28), are attracting neutrophils toward the airways. 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.…”

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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“…These cDC show prominent expression of the Langerhans' cell markers langerin and CD1a and the costimulatory molecules CD80 and CD86 39 . The effects of cigarette smoke on DC production of IL-8 and prostaglandin E2 appears to be mediated via both oxidative stress and the direct effects of nicotine 40 . Lymphoid aggregates are a common feature in COPD and these are often infiltrated by langerin + cDC, especially in those with severe airflow obstruction 41 .…”

Section: Copdmentioning

confidence: 99%