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Vincent Cottin

Publications and source records attributed to Vincent Cottin.

25 records · Page 2Linked to original sources
PubMed2002

[Treatment of pulmonary fibrosis].

A RECENTLY MODIFIED CONCEPT: Idiopathic pulmonary fibrosis (IPF) is characterized by dyspnea on exertion, diffuse radiological infiltrates and alterations in respiratory function. The approach to IPF has recently changed with a more precise definition of the histological diagnostic criteria (hence excluding other disorders such as non-specific interstitial pneumonia), and with the hypothesis that fibro-proliferation and abnormalities in epithelial repair may have a greater physiopathological role than inflammation. DEBATABLE RESULTS FOR CORTICOSTEROIDS: To date, no treatment has demonstrated its efficacy in this disorder and few randomised studies are available. Although early observations showed some benefit of corticosteroids, it is now well established that these studies in fact included a proportion of other corticosteroid-sensitive diseases, such as non-specific interstitial pneumonia. In more recent studies, in which the diagnosis of IPF was made more rigorously, no convincing demonstration of the efficacy of corticosteroids or of immunosuppressive treatments (cyclophosphamide, azathioprine) was made. A trial of corticosteroid therapy for a period of 3 to 6 months (possibly combined with immunosuppressors) is still recommended in the absence of contraindications, but with rigorous and objective assessment of the efficacy, and careful monitoring of the side effects. TREATMENTS UNDER STUDY: Treatments aimed at limiting fibrogenesis have also been proposed. However, clinical studies have not confirmed the initial results obtained with colchicine. Nevertheless, encouraging results have been obtained with other "anti-fibrosing" agents (such as pirfenidone) or immunomodulators (interferon-gamma-1b); such treatment should be further evaluated by larger, randomised, controlled trials in order to know whether these results are applicable to a less selected population. BETWEEN SYMPTOMATIC CARE AND TRANSPLANTATION: In the absence of effective treatment, the management of IPF, the diagnosis of which has been confirmed by rigorous criteria (ideally lung biopsy) is primarily symptomatic. Young patients should be assessed with a view of pulmonary transplantation.

Adjuvants, Immunologic↗
PubMed2002

Restricted localization of the TNF receptor CD120a to lipid rafts: a novel role for the death domain.

The TNF-alpha receptor, CD120a, has recently been shown to be localized to both plasma membrane lipid rafts and to the trans Golgi complex. Through a combination of both confocal microscopy and sucrose density gradient ultracentrifugation, we show that amino acid sequences located within the death domain (DD) of CD120a are both necessary and sufficient to promote the appropriate localization of the receptor to lipid rafts. Deletion of the DD (CD120a.Delta321-425) prevented the receptor from being targeted to lipid rafts and resulted in a uniform plasma membrane localization. A similar loss of raft localization was also observed following pairwise deletion of the six alpha-helices that comprise the DD. In all situations, the loss of the ability of CD120a to become localized to lipid rafts following mutagenesis was paralleled by a failure of the receptor to initiate apoptosis. Furthermore, introduction of the lpr mutation into CD120a (CD120a.L351N) also resulted in both a loss in the ability of the receptor to signal apoptosis and to be appropriately localized to rafts. In contrast to CD120a, CD120b, which lacks a DD, is mainly expressed in the bulk plasma membrane and to a lesser extent in lipid rafts, but is absent from the Golgi complex. However, a chimeric receptor in which the DD of CD120a was fused to the cytoplasmic domain of CD120b was predominantly localized to lipid rafts. Collectively, these findings suggest that in addition to its role in CD120a signaling, an appropriately folded and functionally active DD is required for the localization of the receptor to lipid rafts.

Antigens, CD↗
PubMed2002

Impairment of macrophage survival by NaCl: implications for early pulmonary inflammation in cystic fibrosis.

Inflammation, characterized by the presence of proinflammatory chemokines and neutrophils, is a hallmark of early airway disease in infants with cystic fibrosis (CF), although the underlying mechanisms remain poorly defined. In this study, we evaluated the role of NaCl and the ensuing hyperosmolar effect on tumor necrosis factor (TNF)-alpha signaling and apoptosis in macrophages. Incubation of mouse macrophages with NaCl activated p38(mapk) and the p46(jnk) and p54(jnk) c-jun NH(2)-terminal kinase isoforms, but not p42(mapk/erk2) or Akt. Similar results were obtained with sorbitol, suggesting a general response to hyperosmolarity. Strikingly, the activation of p42(mapk/erk2) and Akt by TNF-alpha was also inhibited in the presence of NaCl. Because the activation of p42(mapk/erk2) and Akt has been associated with survival responses, we investigated the effect of NaCl on macrophage apoptosis. The results indicated a synergistic increase in apoptosis when macrophages were exposed to TNF-alpha in the presence of NaCl compared with stimulation with TNF-alpha alone or NaCl alone. Furthermore, pharmacological inhibition of p42(mapk/erk2) and Akt mimicked the effect of NaCl. Collectively, these findings indicate that modest elevations in NaCl differentially regulate the activation of mitogen-activated protein kinases and Akt and potentiate macrophage apoptosis. We speculate that augmentation of macrophage apoptosis in CF airways may result in decreased clearance of neutrophils and in deficiencies in the elimination of common CF pathogens.

Animals↗
PubMed2002

[Induced interstitial pneumonitis: role of pegylated interferon alpha 2b].

Pulmonary complications of alpha interferon are rare. We report two cases of lung complications in liver transplantation patients for HCV related cirrhosis. After switching from interferon alpha to pegylated interferon alpha 2b, one patient developed a BOOP (Bronchiolitis Obliterans Organizing Pneumonia) and the other severe interstitial pneumonitis. We discuss the causes of these rare pulmonary alpha-interferon induced complications and the different way to suggest that the pegylated interferon alpha 2b could be related to the risk of pulmonary toxicity of this treatment.

Adult↗