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P Soler

Publications and source records attributed to P Soler.

At least 55 records · Page 3Linked to original sources
PubMed1994

Interleukin 6 secretion by monocytes and alveolar macrophages in systemic sclerosis with lung involvement.

Interleukin-6 (IL-6) has been involved in the pathogenesis of inflammatory and/or autoimmune diseases. We characterized the production of IL-6 by blood monocytes and alveolar macrophages (AM) in 11 patients with definite systemic sclerosis (SSc) with lung involvement and in eight normal control subjects. IL-6 levels were determined in serum, bronchoalveolar lavage (BAL) supernatants, monocytes, and AM cell culture supernatants using an ELISA kit. BAL cell analysis evidenced an alveolitis with hypercellularity and increased neutrophils and mast cells absolute counts. Serum and BAL IL-6 levels were low and similar in SSc and control groups. The monocytes of the group with SSc secreted more IL-6 than did the control group, both spontaneously (p = 0.01) and after LPS stimulation (p = 0.0007). Spontaneous secretion of IL-6 by AM tended to be higher in the SSc group than in the control group (p = 0.22). LPS-induced IL-6 secretion by AM was similar in both groups. Our study demonstrates that during SSc lung disease, spontaneous and stimulated IL-6 secretion by blood monocytes is increased, compared with secretion by healthy control subjects. By contrast, IL-6 secretion by AM is normal despite evidence of mild alveolitis.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Ultrastructural alterations of the air-blood barrier in sarcoidosis and hypersensitivity pneumonitis and their relation to lung histopathology.

To evaluate the incidence of air-blood barrier lesions in the course of chronic interstitial lung diseases, we studied by electron microscopy open lung biopsy specimens from patients with sarcoidosis or chronic hypersensitivity pneumonitis, and compared the distribution of ultrastructural air-blood barrier lesions (including swelling or destruction of epithelial and endothelial cells, type II cell hyperplasia, and basement membrane disruption) with the type of histopathologic abnormalities present (including inflammation, inflammation and fibrosis, or fibrosis alone). Ultrastructural lesions of the air-blood barrier were frequently observed in sarcoidosis as well as hypersensitivity pneumonitis. Their nature and distribution were highly dependent on the histologic pattern of lung tissue in which they were present: epithelial and/or endothelial injury was more frequently observed in inflammatory areas (90 to 100% of all lung specimens displaying inflammation alone), whereas type II cell hyperplasia was mainly identified in fibrotic tissues (83 to 100% of all lung specimens displaying fibrosis alone). Strikingly, in lung tissue considered as normal by light microscopy, air-blood barrier was frequently found to be damaged (50 to 62% of apparently normal lung specimens), suggesting that alveolar lesions may constitute an early phenomenon in the course of pulmonary inflammatory processes. The air-blood barrier alterations observed in this study may provide an anatomic basis for the modifications of alveolar permeability described in pulmonary sarcoidosis and hypersensitivity pneumonitis.

Adult↗
PubMed1994

Interleukin-8 and neutrophils in systemic sclerosis with lung involvement.

We investigated the mechanisms and consequences of neutrophil accumulation in the airspace in 11 patients with systemic sclerosis (SSc) and interstitial lung disease. Seven normal subjects served as controls. We measured total neutrophil elastase burden, elastase activity, and alpha-1-antitrypsin (alpha 1AT) in bronchoalveolar lavage (BAL) fluid and we evaluated the in vitro interleukin-8 (IL-8, a potent chemoattractant for neutrophils) secretion by alveolar macrophages (AM). A mild neutrophil alveolitis was observed in patients when compared with control subjects. Total BAL elastase burden was higher in patients than in control subjects and correlated positively with the percentage of neutrophils in BAL. BAL elastase activity was undetectable in control subjects, but it was detected in all patients but one (mean: 257 +/- 87 mU/L). Spontaneous IL-8 secretion by AM was higher in patients with SSc than in control subjects (518 +/- 115 versus 228 +/- 65 ng/ml, p = 0.04) and positively correlated with the percentage of neutrophils in BAL (r = 0.505). We conclude that (1) the neutrophil could participate in the pathogenesis of SSC lung disease through the release of elastase; (2) the AM could contribute to the influx of neutrophils in the alveolus through the release of IL-8.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Expression of heat shock proteins in human lung and lung cancers.

Heat shock proteins (HSP) are highly conserved molecules whose expression is induced in eukaryotic cells following a broad spectrum of environmental stresses. These proteins can also be expressed by virally transformed cells and cancer cells and are important targets for T lymphocytes. Little is known about the abundance and distribution of HSP in the normal lung, the effect of cigarette smoking on their expression, or their expression in human lung carcinomas. We have used monoclonal antibodies coupled with immunohistochemical and immunoelectrophoretic techniques to evaluate the distribution of four different HSP (HSP 90 kD, HSP 73 kD/constitutive, HSP 72 kD/inducible, and HSP 63 kD) in normal lung (n = 14) and lung cancers (n = 15). In lung tissue from nonsmokers (n = 7), bronchiolar epithelial cells were intensely positive for HSP 90 kD and HSP 72 kD/inducible and weakly reactive for HSP 63 kD. Most macrophages also expressed these HSP at low levels, but no other parenchymal or immune/inflammatory cells were positive. Cigarette smoking did not modify the distribution or the intensity of HSP in bronchiolar epithelial cells, and macrophages from smokers expressed similar or lower levels of these HSP. Tumor cells from 14 of 15 lung carcinomas expressed one or more of the HSP. Considerable heterogeneity in the expression of HSP by cells in a given tumor was observed, explained in part by differences in the differentiation of the cells. Detection of HSP by immunohistochemical and immunoelectrophoretic techniques gave similar results for HSP 72 kD/inducible and HSP 90 kD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Persistent asthma after inhalation of a mixture of sodium hypochlorite and hydrochloric acid.

Chlorine gas inhalation can lead to temporary mucous membrane irritation, pulmonary edema, and transient bronchospasm. Existence of respiratory sequelae is debated. We report a case of asthma, persisting 2 years after the inhalation of a mixture of sodium hypochlorite and hydrochloric acid. Bronchial histologic findings and transmission electron microscopy examinations showed uncommon abnormalities supporting irritation for cause of this nonimmunologic asthma.

Accidents, Home↗
PubMed1993

Middle ear cell line that maintains vectorial electrolyte transport.

The middle ear epithelium plays a major role in keeping the temporal bone cavities fluid-free and air-filled, which is a mandatory condition to allow optimum transmission of the sound vibrations from the tympanic membrane to the inner ear. Previous works have recently established the absorptive function of the middle ear epithelium, using primary cultures derived from Mongolian gerbil (Meriones unguiculatus). Because of the paucity of cells as obtained by enzymatic digestion, we developed a middle ear cell line (MESV) using wild-type SV40 infection of primary culture of Mongolian gerbil's middle ear epithelial cells. Transformation was attested by nuclear expression of SV40 large T antigen, prolonged in vitro passages (presently beyond 50 passages), and tumor-inducing ability when subcutaneously injected in athymic mice. Transport properties were evaluated after the fifteenth passage. MESV cells retained most cardinal properties of the original middle ear epithelial cells: cell polarization was evidenced by the presence of mature junctional complexes that separate the cell membrane in two distinct domains, with apical microvilli at the luminal side, and by vectorial sodium transport responsible for the transepithelial lumen-negative potential difference (-9.3 +/- 0.14 mV in culture conditions (n = 9), -2.1 +/- 0.25 mV after overnight growth factors and serum deprivation). Short-circuit current was, like in primary cultures, mainly related to a sodium transport occurring through amiloride-sensitive apical sodium channels, since apical addition of amiloride (10(-5) M) reduced ISC from 7.0 +/- 1.4 to 0.6 +/- 0.1 microA/cm2 (P < 0.01, n = 6). Cellular cAMP content was increased by isoproterenol and prostaglandin E2 from 40.5 +/- 5.6 to 258.5 +/- 17.3 and 55.6 +/- 6.2 pmol/mg protein per 5 min, respectively (P < 0.05, n = 10). Isoproterenol and prostaglandin E2 increased ISC with very similar maximal effects: isoproterenol (10(-4) M) increased ISC from 5.73 +/- 0.31 to 12.77 +/- 0.39 microA/cm2, while prostaglandin E2 increased ISC from 5.47 +/- 0.21 to 12.87 +/- 0.42 (n = 3). Since amiloride (10(-5) M) abolished this stimulation, this may be related to an increase of the electrogenic sodium transepithelial transport. The MESV cell line could provide an interesting tool as a model of middle ear epithelial cells for the study of pathophysiological modulations of ion transport.

Amiloride↗
PubMed1993

Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Aged↗
PubMed1993

Surface phenotype of Langerhans cells and lymphocytes in granulomatous lesions from patients with pulmonary histiocytosis X.

Pulmonary histiocytosis X (HX) is a disorder characterized by the presence of granulomas in which Langerhans cells (LC) and lymphocytes are abundant. Although the pathogenesis of pulmonary HX remains unknown, an uncontrolled immune response initiated by LC, which are potent antigen-presenting cells in vitro, may play an important role. To further characterize LC and lymphocytes present in granulomas from these patients, we used immunohistochemical techniques and monoclonal antibodies to evaluate the surface phenotype and electron microscopy (EM) to seek evidence for close interactions between both cell types in these lesions. In all samples, HX granulomas contained large numbers of strongly positive CD1a cells in which typical Birbeck granules were identified by EM. The number of Birbeck granules in LC from HX granulomas was strikingly increased compared with that in LC in the bronchioles of normal subjects. Furthermore, unlike normal LC, essentially all LC in HX granulomas expressed CD4 antigens and were strongly positive for CD1c. Lymphocytes infiltrating HX granulomas were almost entirely CD3+ T cells and were mainly CD4 positive (CD4/CD8 ratio 3.7 +/- 1.3). These T lymphocytes expressed almost exclusively alpha/beta T cell receptors, and gamma/delta T cells were rarely observed (< 5% of CD3+ cells). In areas of lymphocytic infiltration, close differentiated contacts between LC and lymphocytes were observed by EM in all samples. These results demonstrate that interactions between activated LC and CD4+ T lymphocytes are prominent in early HX granulomas and support the idea that an immune response in which LC serve as accessory cells is involved in the pathogenesis of this disorder.

Adult↗
PubMed1993

Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.

GM-CSF has been shown to be important for the survival and function of cells of dendritic cell/Langerhans cell (LC) lineage in vitro. Since these cells have been demonstrated to infiltrate human lung and some lung carcinomas, we hypothesized that the production of GM-CSF in the lung could be important in their recruitment and differentiation. Using both immunohistochemistry and in situ hybridization, we have shown that: (a) GM-CSF was produced by normal bronchiolar epithelium, the only site were CD1a+ LC are observed in the normal lung, whereas neither GM-CSF production nor LC were identified in normal alveolar epithelium. (b) In inflamed pulmonary tissue, hyperplastic alveolar cells produced GM-CSF, and CD1a+ LC accumulated adjacent to these cells. (c) Some, but not all, lung carcinomas produced this cytokine, and a close correlation was found between the production of GM-CSF and the number of CD1a+ LC infiltrating these tumors. Since GM-CSF was produced at all sites where CD1a+ LC are known to accumulate, but not at other locations within the lung, these data suggest that the local production of GM-CSF by certain lung cells may play an important role in determining the distribution and differentiated state of dendritic cell/LC in the human lung.

Adenocarcinoma↗
PubMed1993

Primary culture of Reissner's membrane from the gerbil: growth, morphologic features, and characterization.

To overcome the technical difficulties encountered in investigating the physiology of Reissner's membrane (RM), primary culture of RM was established. Minute explants obtained by mechanical dissociation were seeded on impermeable substrate coated with collagen type I in serum-free, hormone-supplemented medium. Within 2 weeks, a large cultured area was obtained which reproduced the two cell layers of the original explant. One layer, deep or superficial depending on the side to which the explant adhered, was made of cells exhibiting light and electron microscopy characteristics of an epithelium. Immunohistochemical methods revealed that they expressed cytokeratin, demonstrating their epithelial nature. The second layer was made of mesenchymal cells. This study suggests that cell culture of RM will facilitate further investigation of its physiology.

Animals↗
PubMed1993

[Physiology of granulomas].

Granulomas are a local formation of specific cells including macrophages and lymphocytes revealing a chronic inflammatory reaction against infection, often due to intracellular agents. Granulomas can be composed of macrophages (foreign body reaction), epithelioid cells (immune granulomas of sarcoidosis, tuberculosis), or Langerhans' cells (histiocytosis X). In immune granulomas, the epithelioid cells derived from activated macrophages are found at the centre of the granuloma associated with CD4+ T-lymphocytes, while the periphery is mainly populated with CD8+ T-lymphocytes. Granulomas are not static formations, the rate of cell turnover is high. Different cytokines have been identified as mediators involved in the formation and maintenance of these granulomas: IL2, interferon gamma, TNF alpha, 1,25(OH)2D3, IL1. Major questions, especially concerning antigens involved in granulomatous reactions, remain to be answered for a better understanding of these events.

Cell Cycle↗
PubMed1992

Lymphocytes infiltrating normal human lung and lung carcinomas rarely express gamma delta T cell antigen receptors.

It has been suggested that T lymphocytes expressing gamma delta T cell receptors (TCR) could play an important role in the defence of epithelia against infection and neoplastic transformation, but the potential for gamma delta T lymphocytes to serve these functions in human respiratory epithelium has received little attention. In this study, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number and distribution of T lymphocytes expressing alpha beta and gamma delta TCR in normal human lung and in lung carcinomas. T lymphocytes present in normal bronchi and alveolar parenchyma were predominantly of the alpha beta TCR phenotype, whereas gamma delta T lymphocytes represented only 1.1 +/- 0.7% and 1.3 +/- 0.5% of total CD3+ lymphocytes respectively. An important lymphocytic infiltration was noted in the stroma of all primary lung carcinomas examined, and some T lymphocytes were also present infiltrating between tumour cells. These T lymphocytes were almost entirely alpha beta T cells and only rare gamma delta T cells were found, regardless of the histologic type of carcinoma (0.8 +/- 0.1% of CD3+ T cells). This study demonstrates that T cells present in normal bronchi and lung parenchyma and those infiltrating primary lung carcinomas express predominantly alpha beta TCR. These findings do not support the conclusion that gamma delta T lymphocytes play an important role either in the defence of human lung epithelia or in immune responses directed against primary lung carcinomas.

Adenocarcinoma↗
PubMed1992

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients.

The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/- 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria.

Administration, Oral↗
PubMed1992

Pulmonary Langerhans' cell granulomatosis (histiocytosis X).

Pulmonary Langerhans' cell granulomatosis is usually classified among the lung diseases of unknown origin. Better appreciation of the characteristic clinical features of this disease, more detailed description of the pathologic lesions, and recent advances in the basic biology of Langerhans' cells have provided new insights into the pathogenesis of this process.

Cell Transformation, Neoplastic↗
PubMed1992

Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation.

Mechanical ventilation with high or even moderate peak inspiratory pressure produces pulmonary permeability edema. Besides the level of overinflation, duration may affect both severity and type of edema. We studied the effect of 2 min of 35-mmHg peak pressure mechanical ventilation (HV) on microvascular permeability and deep lung fluid balance in rats. It resulted in increased extravascular lung water (+50%), bloodless dry lung weight (+25%), and albumin uptake in lungs (+450%). The increase in dry lung weight and albumin uptake compared with that of lung water suggested major permeability alterations. Ultrastructural examination showed the presence of numerous endothelial blebs. Epithelial lining fluid (ELF) volume, its potassium and protein concentrations, and cellular composition were assessed by bronchoalveolar lavage. There was an increase in ELF volume (+180%), a decrease in ELF potassium concentration (-50%), and an increase in ELF protein content (+76%). A few blood cells were recovered, suggesting the presence of a few large epithelial breaks. Some animals were allowed to recover for periods less than or equal to 180 min after HV. Extravascular lung water, dry lung weight, and albumin distribution space returned to control levels within 45 min. ELF volume diminished but remained larger than in controls, and ELF protein concentration increased probably because of alveolar fluid resorption. No further hemorrhage was observed. These results indicate that periods of HV as short as 2 min transiently alter microvascular permeability in rats.

Animals↗
PubMed1991

[CD8+T-cell lymphocytic alveolitis in sarcoidosis. 4 cases].

We report 4 cases of histologically proven sarcoidosis with lymphocytic alveolitis. The T CD4+/T CD8+ ratio was below 1 in the bronchoalveolar lavage fluid. Since there was no clinical and paraclinical evidence of extrinsic allergic alveolitis or HIV infection, and since 3 of the patients were nonsmokers and the 4th one smoked moderately, we considered that the T CD8+ lymphocytic alveolitis was related to the sarcoidosis. In 3 patients the presence of mediastinal adenopathy suggested that sarcoidosis was of recent onset. The fact that T CD4+/T CD8+ ratio was normal in blood indicated that T CD8+ lymphocytes were predominant only in the lung. Thus, the finding of T CD8+ lymphocytic alveolitis should not exclude a diagnosis of sarcoidosis.

Adult↗
PubMed1991

Sodium-dependent phosphate and alanine transports but sodium-independent hexose transport in type II alveolar epithelial cells in primary culture.

Inorganic phosphate, amino acids and sugars are of obvious importance in lung metabolism. We investigated sodium-coupled transports with these organic and inorganic substrates in type II alveolar epithelial cells from adult rat after one day in culture. Alveolar type II cells actively transported inorganic phosphate and alanine, a neutral amino acid, by sodium-dependent processes. Cellular uptakes of phosphate and alanine were decreased by about 80% by external sodium substitution, inhibited by ouabain (30 and 41%, respectively) and displayed saturable kinetics. Two sodium-phosphate cotransport systems were characterized: a high-affinity one (apparent Km = 18 microM) with a Vmax of 13.5 nmol/mg protein per 10 min and a low-affinity one (apparent Km = 126 microM) with a Vmax of 22.5 nmol/mg protein per 10 min. Alanine transport had an apparent Km of 87.9 microM and a Vmax of 43.5 nmol/mg protein per 10 min. By contrast, cultured alveolar type II cells did not express sodium-dependent hexose transport. Increasing time in culture decreased Vmax values of the two phosphate transport systems on day 4 while sodium-dependent alanine uptake was unchanged. This study demonstrated the existence of sodium-dependent phosphate and amino acid transports in alveolar type II cells similar to those documented in other epithelial cell types. These sodium-coupled transports provide a potent mechanism for phosphate and amino acid absorption and are likely to play a role in substrate availability for cellular metabolism and in regulating the composition of the alveolar subphase. The decrease in phosphate uptake with time in culture is parallel to decrease in surfactant synthesis reported in cultured alveolar type II cells, suggesting that phosphate availability for surfactant synthesis may be accomplished by a sodium-dependent phosphate uptake.

Alanine↗