<scp>PI</scp>3K and<scp>MAPK</scp>s Regulate Neutrophil Migration Toward the Airways in Heaves

Bullone, Michela; Moran, Kantuta; Lavoie‐Lamoureux, A.; Lavoie, Jean‐Pierre

doi:10.1111/jvim.12008

Cited by 14 publications

(8 citation statements)

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“…We studied horses with severe neutrophilic asthma (severe equine asthma, also known as heaves), a condition that shares marked similarities with human neutrophilic asthma [ 25 ], including the remodeling of the ASM layer [ 26 ] and extracellular matrix [ 27 ]. Furthermore, human and equine neutrophils have similar biology [ 4 , 24 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

et al. 2017

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BackgroundSevere neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.MethodsSix neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.ResultsAirway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.ConclusionGC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0689-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

et al. 2017

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“…Optimal results in terms of maximal slope values and sensitivity to increasing concentrations of IL-8 were obtained with 4 10 6 cells/mL (Figure 2B). This cell density is similar to that used in other migration assays with human neutrophils (6 10 6 cells/mL) (21) and equine neutrophils (3 10 6 cells/mL, 2 10 6 cells/mL) (31, 37), and in other impedance-based assays with monocytes and macrophages (8 10 6 cells/mL) (28). Interestingly, increasing concentrations of fibronectin were not associated with higher slope values (i.e., increased neutrophil chemotaxis) (Figure 2C).…”

Section: Resultsmentioning

confidence: 58%

A Real-Time Assay for Neutrophil Chemotaxis

2016

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Neutrophils are the predominant cells during acute phases of inflammation, and it is now recognized that these leukocytes play an important role in modulation of the immune response. Directed migration of these cells to the sites of injury, known as chemotaxis, is driven by chemoattractants present at the endothelial cell surface or in the extracellular matrix (ECM). Since uncontrolled or excessive neutrophil chemotaxis is involved in pathological conditions such as atherosclerosis and severe asthma, studying the chemical cues triggering neutrophil migration is essential for understanding the biology of these cells and developing new anti-inflammatory therapies. Although several methods have been developed to evaluate neutrophil chemotaxis, these techniques are generally labor-intensive or alter the native form of these cells and their physiological response. Here we report a rapid, non-invasive, impedance-based, and label-free assay for real-time assessment of neutrophil chemotaxis.

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“…Consistently, our previous data demonstrate that the migratory response of neural stem cells to SDF-1a showed a typical biphasic dose-response curve (Chen et al 2014). All these findings indicate that MSCs at varying levels of Many studies have shown that PI3K/Akt and MAPK signaling pathways mediate cell migration induced by chemokines or cytokines (Bullone et al 2013;Yang et al 2013;Segarra et al 2006). In the present study, we found that SDF1a altered the phosphorylation of Akt and MAPKs which correlate closely with the differentiation states of MSCs.…”

Section: Discussionmentioning

confidence: 91%

Neural Differentiation of Mesenchymal Stem Cells Influences Their Chemotactic Responses to Stromal Cell-Derived Factor-1α

Xie

et al. 2014

Cell Mol Neurobiol

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Mesenchymal stem cells (MSCs) are proposed as a promising source for cell-based therapies in neural disease. Although increasing numbers of studies have been devoted to the delineation of factors involved in the migration of MSCs, the relationship between the chemotactic response and the differentiation status of these cells is still unclear. In the present study, we demonstrated that MSCs in varying neural differentiation states display various chemotactic responses to stromal cell-derived factor-1α (SDF-1α). The chemotactic responses of MSCs under different differentiation stages in response to SDF-1α were analyzed by Boyden chamber, and the results showed that cells of undifferentiation, 24-h preinduction, 5-h induction, and 18-h maintenance states displayed a stronger chemotactic response to SDF-1α, while 48-h maintenance did not. Further, we found that the phosphorylation levels of PI3K/Akt, ERK1/2, SAPK/JNK, and p38MAPK are closely related to the differentiation states of MSCs subjected to SDF-1α, and finally, inhibition of SAPK/JNK signaling significantly attenuates SDF-1α-stimulated transfilter migration of MSCs of undifferentiation, 24-h preinduction, 18-h maintenance, and 48-h maintenance, but not MSCs of 5-h induction. Meanwhile, interference with PI3K/Akt, p38MAPK, or ERK1/2 signaling prevents only cells at certain differentiation state from migrating in response to SDF-1α. Collectively, these results demonstrate that MSCs in varying neural differentiation states have different migratory capacities, thereby illuminating optimization of the therapeutic potential of MSCs to be used for neural regeneration after injury.

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PI3K andMAPKs Regulate Neutrophil Migration Toward the Airways in Heaves

Cited by 14 publications

References 50 publications

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

A Real-Time Assay for Neutrophil Chemotaxis

Neural Differentiation of Mesenchymal Stem Cells Influences Their Chemotactic Responses to Stromal Cell-Derived Factor-1α

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