Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways

Pignatti, Patrizia; Moscato, Gianna; Casarini, Simona; Delmastro, Monica; Poppa, Mariangela; Brunetti, Giuseppe; Pisati, P.; Balbi, Bruno

doi:10.1016/j.jaci.2004.08.048

Cited by 37 publications

(28 citation statements)

References 29 publications

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“…Previous investigations have demonstrated increased concentrations of IL-8 in bronchoalveolar lavage fluid or serum from patients with severe asthma [16,17,18]. Pignatti et al [19] reported that the expression of the CXCL8/IL-8 receptors CXCR1 and CXCR2 is markedly lower on sputum neutrophils than on peripheral blood neutrophils and that the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with that on sputum neutrophils,suggesting in vivoexposure and usage of those receptors during the migration of neutrophils into the airways. Pepe et al [23] reported that IL-8 expression is increased in airway smooth muscle cells of patients with severe asthma as compared with moderate asthmatics.…”

Section: Discussionmentioning

confidence: 99%

“…The emigration of circulating blood leukocytes into specific sites of immune reaction is not the result of a single molecular event but of complex processes involving adhesion molecules, cytokines and chemoattractants. Among the neutrophil-active chemoattractants described to date, the CXC chemokines, in particular IL-8 (CXCL8), ENA-78 (CXCL5), and GRO-α (CXCL1) have been suggested to contribute to bronchial neutrophilia in asthmatics [13,14,15,16,17,18,19]. …”

Section: Introductionmentioning

confidence: 99%

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Neutrophilic Inflammation and CXC Chemokines in Patients with Refractory Asthma

Kikuchi

Takaku

et al. 2009

Int Arch Allergy Immunol

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Background: There is evidence that eosinophils and neutrophils are simultaneously increased in the airways of some patients with chronic refractory asthma. The mechanisms by which neutrophils accumulate in the airways of asthmatics remain to be elucidated, however, chemoattractants for neutrophils such as CXC chemokines may affect either the accumulation or functional status of neutrophils in such patients. The objective of the present study was to identify the CXC chemokine responsible for the neutrophilic and possibly eosinophilic inflammation observed in the airways of patients with refractory asthma. Methods: Following the inhalation of hypertonic saline, induced sputum was obtained from 14 healthy controls, 16 patients with mild well-controlled nonrefractory asthma, and 14 patients with refractory asthma. Concentrations of CXC chemokines and differential inflammatory cell counts were determined. Results: The percentages of induced sputum eosinophils were significantly higher both in patients with nonrefractory asthma and in patients with refractory asthma. On the other hand, the percentages of neutrophils were increased only in sputum from patients with refractory asthma. The concentration of IL-8, but not ENA-78 or GRO-α, was also significantly increased in induced sputum from patients with refractory asthma. The concentration of IL-8 correlated significantly with the percentages of neutrophils. Conclusions: The results of the present study suggest that IL-8, but not ENA-78 or GRO-α, may contribute to the observation of neutrophilic inflammation in patients with refractory asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutrophilic Inflammation and CXC Chemokines in Patients with Refractory Asthma

Kikuchi

Takaku

et al. 2009

Int Arch Allergy Immunol

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“…CCL2 and CCL3 levels were also demonstrated to be consistently elevated in the BALF of ARDS patients, although they did not correlate with either neutrophil or macrophage numbers (63). In addition, it has been reported that human neutrophils downregulate CXCR1 and CXCR2 after recruitment to the airways (144), which may have important consequences for the therapeutic inhibition of these receptors in lung disease. Indeed, human neutrophils have been shown to undergo rapid gene expression changes following transepithelial migration, resulting in delayed apoptosis and reduced capacity for IL-8-mediated chemotaxis (36).…”

Section: Other Chemokines Involved In Neutrophil Migrationmentioning

confidence: 99%

The mercurial nature of neutrophils: still an enigma in ARDS?

Williams

Chambers

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

356

304

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“…7 The potential effects of monocyte activation include systemic inflammation with elevated monocyte derived cytokines in the peripheral blood and oxidative stress, which has previously been associated with asthma and, especially, neutrophilic asthma. 9 Differences in the phenotype and function of monocytes may be associated with environmental factors. 10 Therefore, an alteration in the epigenome is a likely underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%