Biomedical subjects

Paul Soler

Publications and source records attributed to Paul Soler.

5 recordsLinked to original sources

PubMed2003

Defect of hepatocyte growth factor secretion by fibroblasts in idiopathic pulmonary fibrosis.

Hepatocyte growth factor (HGF) is a growth factor that protects alveolar epithelial cells from pulmonary fibrosis in various animal models. We compared in vitro HGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 8) and from control subjects (n = 6). Basal HGF secretion by IPF fibroblasts was decreased by 50% when compared with control fibroblasts (p < 0.05). HGF was secreted mainly in the cleaved mature form, both in IPF and control fibroblasts. HGF messenger RNA levels were reduced in IPF fibroblasts. Prostaglandin (PG) E2 secretion by IPF fibroblasts was low when compared with control subjects (p < 0.05). After the addition of PGE2 (10-6 M) or dibutyryl cyclic AMP (10-3 M), HGF secretion by IPF fibroblasts reached the level of control subjects. Inhibition of PGE2 synthesis with indomethacin reduced HGF secretion by control fibroblasts but had no effect on IPF fibroblasts. HGF secretion by control fibroblasts was also slightly inhibited by transforming growth factor (TGF)-beta1 and stimulated by anti-TGF-beta antibody, whereas both agents had no effect on IPF fibroblasts. Our results demonstrate a defect in HGF production by IPF fibroblasts that seems secondary to a defect in PGE2 secretion.

Adult↗

PubMed2003

Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death.

Increased numbers of tumor-infiltrating neutrophils are linked to poorer outcome in patients with adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype. Hepatocyte growth factor (HGF) is a pleiotropic cytokine operating through activation of the proto-oncogene c-met and is a factor of poor prognosis in various cancers. Reports that neutrophils produce HGF led us to investigate their participation in the aerogenous spread of tumor cells and the prognosis of BAC, through the effect of HGF on c-met-expressing tumor cells. Immunoreactive HGF was detected in bronchoalveolar lavage fluid (BALF) supernatants from 34 of 36 patients, whereas it was undetectable in BALF from healthy controls. The HGF thus detected was locally produced, because HGF mRNA was expressed by the patients' fresh alveolar cells, and HGF protein was detected in 24-h culture supernatants. In immunocytochemical studies of BALF cytospin preparations and tumor specimens from the patients, neutrophils were always HGF-positive, whereas alveolar macrophages and tumor cells gave inconsistent results. Alveolar neutrophil-derived HGFs induced significant, concentration-dependent migration of BAC-derived tumor cells in vitro, and this effect was inhibited by anti-HGF neutralizing antibodies. Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha (present in the lung tumor microenvironment) provoked HGF release from neutrophil intracellular stocks, and the capacity of blood neutrophils from BAC patients to produce HGF was unaltered. Immunochemical studies of c-met expression in BALF cytospin preparations and tumor sections showed that most HGF receptor-bearing cells were tumor cells. High HGF levels in BALF supernatants were significantly associated with poorer outcome in patients with BAC and were an independent predictor of clinical outcome in multivariate analysis. Altogether, our results support the notion that BAC generates a local environment that attracts functionally normal neutrophils from peripheral blood and leads to neutrophil release of biologically active HGF on contact with HGF receptor-expressing tumor cells, thereby contributing to poorer patient outcome.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2002

Three-dimensional characterization of pathologic lesions in pulmonary langerhans cell histiocytosis.

The characteristic lesions of pulmonary Langerhans cell histiocytosis (LCH) associate destructive granulomas containing large numbers of Langerhans cells and cysts. The lesions are usually considered to develop around small airways, and cysts are thought to result from destruction of the bronchiolar wall by the granulomatous reaction. However, the extent to which the granulomatous reaction is truly bronchocentric remains unknown, and the mode of formation of the cysts has not been defined. By using serial sections, this study aimed to explore further the relationships between pulmonary LCH lesions and distal airways, and the development of cysts. The results demonstrated that the granulomatous process of pulmonary LCH affected exclusively small airways, in an acinar distribution. The lesions extended without interruption along the bronchiolar axis, forming a continuous sheath around distal airways. The granulomatous reaction seemed to progress along the bronchiolar axis over time, extending the abnormalities in both the proximal and distal directions. Cystic lesions resulted from the destruction of the bronchiolar wall and progressive dilatation of the lumen, subsequently circumscribed by fibrous tissue. Because pulmonary LCH lesions affect and progressively destroy distal airways, it may be proper to consider the disease a bronchiolitis rather than an interstitial lung disorder.

Adult↗

PubMed2002

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

Algorithms↗

PubMedDate not supplied

Diesel particles are taken up by alveolar type II tumor cells and alter cytokines secretion.

Diesel exhaust particles can reach the alveolar space and interact with alveolar type II cells. The authors investigated whether diesel exhaust particles lead to an internalization process and alter the production of proinflammatory cytokines, such as interleukin-8 and granulocyte macrophage-colony-stimulating factor by human alveolar type II cells. Cells from the human lung epithelial cell line A-549 were incubated with diesel exhaust particles or with inert particles for different periods of time. Phagocytosis was studied with electron microscopic analysis and flow cytometry. Cytokines were quantified in supernatants with enzyme-linked immunosorbent assay. Both diesel exhaust particles and inert particles were similarly engulfed by alveolar type II cells. Diesel exhaust particles induced a dose- and a time-dependent increase in granulocyte macrophage-colony-stimulating factor release and a transient inhibition of interleukin-8 release, but inert particles did not. Diesel exhaust particles were taken up by alveolar type II cells, and they altered cytokine production. Alveolar type II cells, therefore, may represent a target site for the deleterious effects of diesel exhaust particles.

Carbon↗