Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?

D’hulst, An I.; Maes, Tania; Bracke, Ken R.; Demedts, Ingel K.; Tournoy, Kurt G.; Joos, Guy; Brusselle, Guy

doi:10.1186/1465-9921-6-147

Cited by 96 publications

(94 citation statements)

References 33 publications

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“…In contrast to the data presented in this study and the observations of others (16,35,36), there is some data suggesting that NK cells may be functionally suppressed in COPD. However, the interpretation of these reports is limited by small samples sizes, the use of non-COPD smokers with unknown patient characteristics, or in vitro treatment of PBMCs with Cs extract (55,56).…”

Section: Discussioncontrasting

confidence: 55%

“…Additional evidence implicating NK cells in the development of COPD comes from studies on immunocompromised mice exposed to CS (35,36). It has been demonstrated that, in the absence of T cells and B cells, the development of COPD phenotypes still occurred following chronic CS exposure (35,36). In addition, we have recently demonstrated a role for the innate functions of cytotoxic lymphocytes in the pathogenesis of COPD (6).…”

Section: Discussionmentioning

confidence: 99%

“…However, the in vivo relevance of NK cell priming is a limitation of this work and requires further study. Additional evidence implicating NK cells in the development of COPD comes from studies on immunocompromised mice exposed to CS (35,36). It has been demonstrated that, in the absence of T cells and B cells, the development of COPD phenotypes still occurred following chronic CS exposure (35,36).…”

Section: Discussionmentioning

confidence: 99%

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Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Motz¹,

Eppert²,

Wortham³

et al. 2010

The Journal of Immunology

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Chronic obstructive pulmonary disease (COPD) is a debilitating, progressive lung disease punctuated by exacerbations of symptoms. COPD exacerbations are most often associated with viral infections, and exposure to cigarette smoke (CS) followed by viral infection has been shown experimentally to enhance lung inflammation, tissue destruction, and airway fibrosis. Despite this, however, the cellular mechanisms responsible for this effect are unknown. In this study, we examined NK cell function in a mouse model of COPD given the vital role of NK cells following viral infection. Ex vivo stimulation of lung leukocytes with poly(I:C), ssRNA40, or ODN1826 enhanced production of NK cell-derived IFN-γ in CS-exposed mice. NK cells from CS-exposed mice exhibited a novel form of priming; highly purified NK cells from CS-exposed mice, relative to NK cells from filtered air-exposed mice, produced more IFN-γ following stimulation with IL-12, IL-18, or both. Further, NK cell priming was lost following smoking cessation. NKG2D stimulation through overexpression of Raet1 on the lung epithelium primed NK cell responsiveness to poly(I:C), ssRNA40, or ODN1826 stimulation, but not cytokine stimulation. In addition, NK cells from CS-exposed mice expressed more cell surface CD107a upon stimulation, demonstrating that the NK cell degranulation response was also primed. Together, these results reveal a novel mechanism of activation of the innate immune system and highlight NK cells as important cellular targets in controlling COPD exacerbations.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Motz¹,

Eppert²,

Wortham³

et al. 2010

The Journal of Immunology

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“…Our findings are in contrast of those by d'Hulst et al (25) demonstrating that Scid mice are not protected from cigarette smoke-induced emphysema, however, the complete lack of an immune system and ability to generate an inflammatory cell response make this a less than ideal model.…”

Section: Figurecontrasting

confidence: 56%

CD8+ T Cells Are Required for Inflammation and Destruction in Cigarette Smoke-Induced Emphysema in Mice

Maeno

Houghton

Quintero

et al. 2007

The Journal of Immunology

253

197

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Increased numbers of T lymphocytes are observed in the lungs of patients with chronic obstructive pulmonary disease, but their role in the disease process is not known. We investigated the role of CD8+ T cells in inflammatory cell recruitment and lung destruction in a cigarette smoke-induced murine model of emphysema. In contrast to wild-type C57BL/6J mice that displayed macrophage, lymphocyte, and neutrophil recruitment to the lung followed by emphysema in response to cigarette smoke, CD8+ T cell-deficient (CD8−/−) mice had a blunted inflammatory response and did not develop emphysema when exposed to long-term cigarette smoke. Further studies supported a pathogenetic pathway whereby the CD8+ T cell product, IFN-γ-inducible protein-10, induces production of macrophage elastase (matrix metalloproteinase 12) that degrades elastin, both causing lung destruction directly and generating elastin fragments that serve as monocyte chemokines augmenting macrophage-mediated lung destruction. These studies demonstrate a requirement for CD8+ T cells for the development of cigarette smoke-induced emphysema and they provide a unifying pathway whereby CD8+ T cells are a central regulator of the inflammatory network in chronic obstructive pulmonary disease.

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“…In murine models of cigarette smoke exposure, there are conflicting results as to whether DC numbers are increased or decreased in the lung in response to cigarette smoke. 19,20 In the human lung, four subsets of pulmonary DCs have been identified: myeloid DC 1, myeloid DC 2, plasmacytoid DC, and CD1a ϩ DCs. 21 In chronic asthmatics, CD1a…”

mentioning

confidence: 99%

CC Chemokine Receptor 5 and CXC Chemokine Receptor 6 Expression by Lung CD8+ Cells Correlates with Chronic Obstructive Pulmonary Disease Severity

Freeman

Curtis

Chensue

2007

The American Journal of Pathology

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؉ effector memory phenotype. CD1a؉ DCs produced the respective ligands for CCR5 and CXCR3, CCL3 and CXCL9, and levels correlated with disease severity. CD1a؉ DCs also constitutively expressed the CXCR6 ligand, CXCL16. In conclusion, we have identified major chemokine elements that potentially mediate CD8 ؉ T-cell infiltration during COPD progression and demonstrated that CD1a ؉ mucosal-associated DCs may sustain CD8 ؉ T-cell recruitment/ retention. Chemokine targeting may prove to be a viable treatment approach.

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Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?

Cited by 96 publications

References 33 publications

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

CD8+ T Cells Are Required for Inflammation and Destruction in Cigarette Smoke-Induced Emphysema in Mice

CC Chemokine Receptor 5 and CXC Chemokine Receptor 6 Expression by Lung CD8+ Cells Correlates with Chronic Obstructive Pulmonary Disease Severity

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