Adoptive Transfer of Alveolar Macrophages Abrogates Bronchial Hyperresponsiveness

Careau, Eric; Bissonnette, Élyse

doi:10.1165/rcmb.2003-0229oc

Cited by 94 publications

(90 citation statements)

References 31 publications

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“…Although they are well known to suppress T cell activation and antigen presentation activities of dendritic cells (22,41), their role in asthma is still debated. Using the liposome-mediated macrophage suicide technique (47), we have demonstrated that AM depletion of allergen-sensitized animals leads to airway hyperresponsiveness after allergen challenge (7). These data suggest that AM are essential for the prevention of airway hyperresponsiveness development.…”

mentioning

confidence: 80%

“…Group 1 represents the negative and positive controls, whereas group 2 was used to verify the effect of AM depletion using clodronate (Cl 2MDP; Sigma Chemical)-liposomes 17 days after sensitization (47). AM transfer (groups 3 and 4) was performed as previously described (7). Briefly, bronchoalveolar lavage (BAL) was done 20 days after sensitization, and 2 ϫ 10 6 cells were transferred by intratracheal intubation to rats that had received Cl 2MDP-liposomes 3 days earlier using the same technique.…”

Section: Methodsmentioning

confidence: 99%

“…Ovalbumin (OVA)-sensitized Brown Norway rats produce high levels of IgE and develop both early and late-phase airway responses after allergen challenge (17,18,24). Using this animal model of airway hyperresponsiveness, we have demonstrated that transfer of AM from allergyresistant Sprague Dawley rats to AM-depleted Brown Norway rats reduced airway responsiveness to the level of Sprague Dawley rats in a dose-dependent manner (7). In contrast, transfer of AM from Brown Norway rats to Sprague Dawley rats did not modulate airway responsiveness.…”

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confidence: 99%

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Antigen sensitization modulates alveolar macrophage functions in an asthma model

Careau¹,

Proulx²,

Pouliot³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-We have previously demonstrated that adoptive transfer of alveolar macrophages from allergy-resistant rats to alveolar macrophage-depleted allergic rats prevents airway hyperresponsiveness development, suggesting an important role for alveolar macrophages in asthma pathogenesis. Given that ovalbumin sensitization can modulate alveolar macrophage cytokine production, we investigated the role of sensitized and unsensitized alveolar macrophages in an asthma model. Alveolar macrophages from unsensitized or sensitized Brown Norway rats were transferred to alveolar macrophage-depleted sensitized rats 24 h before allergen challenge. Airway responsiveness to methacholine and airway inflammation were measured the following day. Methacholine concentration needed to increase lung resistance by 200% was significantly higher in alveolar macrophage-depleted sensitized rats that received unsensitized alveolar macrophages compared with alveolar macrophage-depleted sensitized rats that received sensitized alveolar macrophages. Tumor necrosis factor levels in bronchoalveolar lavage fluid of sensitized rats that received unsensitized alveolar macrophages were significantly lower compared with rats that received sensitized alveolar macrophages. Interestingly, alveolar macrophages of unsensitized animals showed higher phagocytosis activity compared with alveolar macrophages of sensitized rats, suggesting that sensitization modulates alveolar macrophage phagocytosis function. Our data suggest an important role of allergen sensitization on alveolar macrophage function in asthma pathogenesis. airway hyperresponsiveness; cytokine; phagocytosis THE INCIDENCE OF allergic respiratory diseases increased dramatically over the last two decades. The genetic predisposition to develop asthma is now well recognized (20). Numerous studies have also shown the importance of inflammatory cells, such as mast cells, lymphocytes, eosinophils, and neutrophils, as well as Th2 type cytokines in asthma (6,19,32). Interleukin (IL)-4 and IL-13, two Th2 cytokines, are important in immunoglobulin (Ig) class switching to IgE, whereas IL-4 and IL-10 play a crucial role in Th2 cell commitment (9,16,50). In contrast, Th1 cytokines (interferon-␥ and IL-12) protect against asthma development in children (48). Other cytokines, such as tumor necrosis factor (TNF), have been demonstrated to amplify the effect of asthmatic inflammation (29,42). Recently, a role of regulatory T cells (Th3 cells, T R cells, CD4 ϩ CD25 ϩ cells, and natural killer T cells) has been suggested in the control of asthma and allergy, but the specific mechanisms are still unknown (2).Alveolar macrophages (AM) are predominant immune effector cells in the alveolar spaces and conducting airways and play a key role in the immunological homeostasis of the lung (8, 30, 43). Although they are well known to suppress T cell activation and antigen presentation activities of dendritic cells (22,41), their role in asthma is still debated. Using the liposome-mediated macrophage suicide technique (47), we have...

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confidence: 80%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Careau¹,

Proulx²,

Pouliot³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Whereas DC activate T cells and thereby promote inflammation, pulmonary M⌽ suppress these processes (20,21,37,43). It has therefore been suggested that the balance of these two cell types influences the progression of lung inflammation, such as asthma (44,45).…”

Section: Discussionmentioning

confidence: 99%

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Landsman

Varol

Jung

2007

The Journal of Immunology

276

270

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Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, monocytes in the mouse comprise two phenotypically distinct subsets that are Gr1 high CX 3 CR1 int and Gr1 low CX 3 CR1 high , respectively. The question remains whether these populations contribute differentially to the generation of peripheral mononuclear phagocytes. In this study, we track the fate of adoptively transferred, fractionated monocyte subsets in the lung of recipient mice. We show that under inflammatory and noninflammatory conditions, both monocyte subsets give rise to pulmonary dendritic cells. In contrast, under the conditions studied, only Gr1 low CX 3 CR1 high monocytes, but not Gr1 high CX 3 CR1 int cells, had the potential to differentiate into lung macrophages. However, Gr1 high CX 3 CR1 int monocytes could acquire this potential upon conversion into Gr1 low CX 3 CR1 high cells. Our results therefore indicate an intrinsic dichotomy in the differentiation potential of the two main blood monocyte subsets.

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“…Adoptive transfer of macrophages has also been investigated in colitis and airway hyperresponsiveness, with promising results (51,52). Litvack and colleagues also showed that, although not true AMs, stem cell-derived, alveolar-like macrophages improved bacterial and neutrophil clearance in another model of lung injury (49), but further study is required to determine the safety and feasibility of these treatment modalities.…”

Section: Original Articlementioning

confidence: 99%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

580

526

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Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs' effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.Methods: Human monocyte-derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker expression, and augmented phagocytic capacity of human MDMs stimulated with LPS or ARDS BALF. These effects were partially mediated by CD44-expressing EVs. Adoptive transfer of AMs pretreated with MSCderived EVs reduced inflammation and lung injury in LPS-injured mice. Inhibition of oxidative phosphorylation in MDMs prevented the modulatory effects of MSCs. Generating dysfunctional mitochondria in MSCs using rhodamine 6G pretreatment also abrogated these effects.Conclusions: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV-mediated mitochondrial transfer. MSC-induced changes in macrophage phenotype critically depend on enhancement of macrophage oxidative phosphorylation. AMs treated with MSCderived EVs ameliorate lung injury in vivo.

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Adoptive Transfer of Alveolar Macrophages Abrogates Bronchial Hyperresponsiveness

Cited by 94 publications

References 31 publications

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

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