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A Cantin

Publications and source records attributed to A Cantin.

At least 19 recordsLinked to original sources
PubMed2001

Neutrophil-mediated epithelial injury during transmigration: role of elastase.

Neutrophil-mediated injury to gut epithelium may lead to disruption of the epithelial barrier function with consequent organ dysfunction, but the mechanisms of this are incompletely characterized. Because the epithelial apical junctional complex, comprised of tight and adherens junctions, is responsible in part for this barrier function, we investigated the effects of neutrophil transmigration on these structures. Using a colonic epithelial cell line, we observed that neutrophils migrating across cell monolayers formed clusters that were associated with focal epithelial cell loss and the creation of circular defects within the monolayer. The loss of epithelial cells was partly attributable to neutrophil-derived proteases, likely elastase, because it was prevented by elastase inhibitors. Spatially delimited disruption of epithelial junctional complexes with focal loss of E-cadherin, beta-catenin, and zonula occludens 1 was observed adjacent to clusters of transmigrating neutrophils. During neutrophil transmigration, fragments of E-cadherin were released into the apical supernatant, and inhibitors of neutrophil elastase prevented this proteolytic degradation. Addition of purified leukocyte elastase also resulted in release of E-cadherin fragments, but only after opening of tight junctions. Taken together, these data demonstrate that neutrophil-derived proteases can mediate spatially delimited disruption of epithelial apical junctions during transmigration. These processes may contribute to epithelial loss and disruption of epithelial barrier function in inflammatory diseases.

Adherens Junctions↗
PubMed2000

Oestrogen metabolism in lymphangioleiomyomatosis: catechol-O-methyltransferase pathway is not involved.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is an uncommon lung disease for which no effective method of treatment has been found. The predilection of LAM for premenopausal women has led to the assumption that hormonal factors play an important role in the pathogenesis of this disease. The aim of this study was to determine if women with LAM manifest alterations in the catechol-O-methyltransferase (COMT) pathway which is essential for preventing the generation of oestrogen derived reactive oxygen species (ROS). METHODS: Blood samples were collected from 15 women with LAM and compared with appropriate controls. The distribution of high and low activity alleles of COMT was determined with a PCR based RFLP assay. The enzymatic activity of COMT was measured in each sample and the potential presence of a circulating inhibitor of COMT was determined. Since an alteration in the COMT pathway could increase the oxidative stress, the plasma concentration of malondialdehyde (MDA), a secondary product generated from lipid peroxidation, has been used as an internal marker. RESULTS: The distribution of high and low activity alleles of COMT (named COMT(HH), COMT(LL), and COMT(HL)) was similar in the two groups with proportions of 40%, 7%, and 53%, respectively, in the women with LAM and 38%, 6%, and 56% in the control subjects. The mean (SD) COMT activity was 24.2 (12.3) pmol/min/mg protein in women with LAM and 24.1 (6.3) pmol/min/mg protein in the control group. Incubation of plasma from women in the two groups with a preparation of commercial COMT showed that no detectable COMT inhibitor was present. The plasma concentration of MDA in the women with LAM was also not significantly different from control subjects. CONCLUSIONS: This study shows that there are no significant alterations in the COMT pathway of women with LAM. It is therefore unlikely that alterations in oestrogen mediated cell signalling pathways are mediated by oxidants derived from an excess of catecholoestrogens in LAM.

Adult↗
PubMed1999

Glucose stimulates phagocytosis of unopsonized Pseudomonas aeruginosa by cultivated human alveolar macrophages.

Glucose has previously been shown to increase the in vitro phagocytosis of unopsonized Pseudomonas aeruginosa by freshly explanted murine peritoneal macrophages (PM) and cultivated alveolar macrophages (AM). This study examined the effect of glucose on the same phagocytosis process in human AM in order to determine whether this phenomenon is conserved among species. Freshly explanted human AM phagocytosed unopsonized P. aeruginosa at a low level (2 bacteria/macrophage/30 min), whereas mouse AM ingested a negligible number of P. aeruginosa (0.01 bacterium/macrophage/30 min). Glucose had no effect on this or other phagocytic processes in freshly explanted mouse or human AM. However, following in vitro cultivation for 72 h, human AM phagocytosed three to four times more unopsonized P. aeruginosa than did freshly explanted cells, but only in the presence of glucose. This glucose-inducible phagocytic response had also been observed in cultivated murine AM. Although similar increases were also detected for the phagocytosis of latex particles and complement-coated sheep erythrocytes by cultivated human AM, these processes were not glucose dependent. The lack of response to glucose in freshly explanted mouse AM was attributed to insufficient glucose transport; however, freshly explanted human AM exhibited significant facilitative glucose transport activity that was inhibitable by cytochalasin B and phloretin. Taken together, these results suggest that the process of glucose-inducible phagocytosis of unopsonized P. aeruginosa is conserved among macrophages from different species, including humans, and that AM, but not PM, required cultivation for this glucose effect to occur. Glucose transport by AM appears to be necessary but not sufficient for phagocytosis of unopsonized P. aeruginosa.

Animals↗
PubMed1998

Proteolytic cleavage of ICAM-1 by human neutrophil elastase.

Human leukocyte elastase (HLE) participates in tissue destruction in a number of inflammatory disorders, including rheumatoid arthritis and cystic fibrosis. Since HLE has been shown to bind to Mac-1, and ICAM-1 plays a key role during the recruitment and the activation of leukocytes at inflamed sites, we investigated the capacity of HLE to cleave ICAM-1. Flow-cytometric analyses showed a dose-dependent cleavage of ICAM-1 by HLE on different human cell lines. The cleavage was completely inhibited by alpha1-antitrypsin, a natural HLE protease inhibitor. The ability of HLE to degrade ICAM-1 was further confirmed by electrophoretic analysis using a soluble form of ICAM-1 (D1-D5). Enzymatic removal of N-linked glycosylation did not significantly modulate ICAM-1 cleavage by HLE, while removal of sialic acid residues partially reduced the sensitivity of ICAM-1 to HLE. We further showed that sputum of cystic fibrosis patients contains high levels of HLE activity capable of cleavage of cell surface ICAM-1. The cleavage induced by incubation of cells with the sputum sample was totally inhibited by alpha1-antitrypsin and the specific peptidic HLE inhibitor N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone. Moreover, the cleavage of ICAM-1 was concomitant to that of CD4 at the surface of the same cell, at the same amplitude, and at all HLE concentrations. The capacity of HLE to modulate the expression of ICAM-1 on the surface of leukocytes by proteolytic cleavage brings support to the hypothesis that overproduction of HLE can cause severe immunologic lung disorders by affecting intercellular adhesion.

Adolescent↗
PubMed1996

Effect of exposure to silica on human alveolar macrophages in supporting growth activity in type II epithelial cells.

BACKGROUND: The proliferative response of type II cells is an important event following silica-induced lung injury. Alveolar macrophages, when activated by fibrogenic agents, secrete various biological mediators which affect cell growth. METHODS: Human alveolar macrophages from normal volunteers were incubated in serum-free medium or in the presence of increasing concentrations of silica. Alveolar macrophage conditioned media were diluted and added to type II cell cultures for proliferation studies. Purified type II pneumocytes were isolated from fetal rat lungs for bioassays. Growth factor activities were partially characterised by size exclusion chromatography. Each fractionated mitogenic peak was preincubated with monoclonal antibody against platelet derived growth factor (PDGF) or antisera against insulin-like growth factor 1 (IGF-1) or fibroblast derived growth factor (FGF) in order to study the nature of each activity. RESULTS: Conditioned media from alveolar macrophages exposed to silica induced an increase in type II cell DNA synthesis and cell number over that seen when type II cells were incubated with unstimulated alveolar macrophage supernatants. Size exclusion of alveolar macrophage supernatants exposed to silica showed four peaks of type II cell stimulating activity with apparent molecular weights of 38, 22, 16, and 8 kDa. Anti-PDGF antibody significantly reduced the activity of the first and second peaks, antiserum against IGF-1 partially reduced the activity of the first and fourth peaks, and antiserum against FGF reduced only the third peak of activity. CONCLUSIONS: Human alveolar macrophages exposed to silica in vitro release mitogens for type II pneumocytes including PDGF-like, IGF-1-like, and FGF-like molecules. These agents are likely to be involved in the epithelial repair and type II cell hyperplasia observed in silicosis.

Adult↗
PubMed1996

Antioxidant activity in bronchoalveolar lavage fluid from patients with lung cancer.

Glutathione (GSH) is one of the key components of the lung antioxidant defenses. Chronic smokers have higher GSH concentrations in their epithelial lining fluid than do nonsmokers. The aim of this study was to compare antioxidant concentrations in epithelial lining fluid (ELF) from nonsmokers, smokers with, and smokers without non-small-cell lung cancer. The study found that GSH in ELF from patients with lung cancer was significantly greater than in ELF from smokers and nonsmokers, at 1,485.5 +/- 208, 544 +/- 97.6 microM, and 339.3 +/- 112 microM, respectively (p < 0.05). In contrast, superoxide dismutase (SOD) was lower in ELF from patients with lung cancer than in that from smokers and nonsmokers, at 3.52 +/- 0.99, 30.82 +/- 8.2, and 43.91 +/- 10.1 U/ml, respectively (p < 0.05). Spontaneous superoxide anion release by adherent alveolar macrophages (AM) showed no difference between smokers with and without lung cancer. These data indicate that patients with lung cancer have marked modifications in their ELF antioxidant defenses by comparison with those of smokers. It is difficult to distinguish whether changed antioxidant status is a primary disturbance involved in the cancer process or whether it is a consequence of the neoplastic changes in malignancy.

Adult↗
PubMed1995

Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro.

Clara cell protein (CC-16, also designated CC-10) is synthesized by the bronchiolar epithelium and has been suggested as an inhibitor of phospholipase A2 (PLA2) activity. Therefore, CC-16 is a candidate for controlling inflammatory events in the lung. Because CC-16 amounts and function may be altered in fibrosing lung diseases in which bronchiolar injury has been reported, it was measured in alveolar fluids and sera. Secretory PLA2 activity in alveolar fluids and the influence of CC-16 on platelet-derived growth factor-induced human fibroblast chemotaxis and cytosolic PLA2 activity were also explored. CC-16 content was decreased in alveolar fluids from idiopathic pulmonary fibrosis (IPF: 1.3 +/- 0.1 mg/L) and bleomycin lung (1.1 +/- 0.2 versus 2.1 +/- 0.2 mg/L in controls, p < 0.05), whereas there was a three- to ninefold increase in secretory PLA2 activity (p < 0.05 versus controls). CC-16 inhibited fibroblast chemotaxis in a dose-dependent manner (90% inhibition at 30 micrograms/ml CC-16). This inhibition was reversed by reducing CC-16. CC-16 was also able to lower fibroblastic cytosolic PLA2 activity by 50% in vitro. In summary, CC-16 is able to inhibit fibroblast chemotaxis in vitro by mechanisms that may be related to a blockage of cytosolic PLA2 activity. It can be postulated that CC-16 deficiency may contribute to fibroblast burden activity in fibrosing lung diseases.

Adult↗
PubMed1995

Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A).

Type II cell hypertrophy with surfactant accumulation in the lung is a common observation in silicosis. Mechanisms leading to these alterations are poorly understood. By using silica dusts and alveolar fluids from saline and silica exposed sheep, we explored four different pathways of surfactant turnover in vitro: (1) synthesis and (2) secretion of lipids by rat type II cells; and dipalmitoylphosphatidylcholine (DPPC) uptake/reuptake by (3) type II cells and (4) alveolar macrophages. Silica had no direct specific effect on type II cell lipid metabolism. Alveolar fluids from both saline and silica exposed animals induced several alterations compared to control medium: (a) an increase in lipid synthesis (60 to 130%, P < 0.05); (b) a decrease in lipid secretion (25 to 70%, P < 0.05); (c) a 50 to 75% increase in DPPC reuptake by type II cells (P < 0.05); (d) a 65 to 75% decrease in DPPC uptake by alveolar macrophages (P < 0.05). DPPC uptake by in vivo silica exposed alveolar macrophages was reduced. Alterations of surfactant lipid metabolism induced by alveolar fluids from silicotic animals was more pronounced than in those treated with control fluids. Anti SP-A antibodies significantly suppressed most of the alveolar fluid induced effects on surfactant turnover. From these in vitro data, silica-induced type II cell hypertrophy seems to result from an increase in lipid synthesis activity and an imbalance in the lipid secretion/reuptake ratio.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Partial characterization of the proliferative activity for fetal lung epithelial cells produced by silica-exposed alveolar macrophages.

The proliferation of lung epithelial cells is a prominent feature of lung tissue response following silica-induced lung injury and alveolar macrophages are recognized as a major contributing cell to the lung inflammatory processes. In previous studies, a growth-promoting activity for fetal rat lung epithelial cells was observed in silicotic alveolar fluids and in supernatants from in vitro and in vivo silica-exposed alveolar macrophages. In the present work, the biological and physicochemical properties of the macrophage-derived growth-promoting activity for fetal lung epithelial cells were explored. Four peaks of growth-promoting activity for lung epithelial cells ranging from 32 to 7 kDa were found in both in vitro and in vivo silica-exposed macrophage supernatants. The investigations were coupled with biochemical treatments of the mitogenic peaks and blocking antibodies or antisera were used to specify further the nature of the proliferative activities. Among the established growth factors, alveolar macrophage-derived growth fractions had characteristics consistent with platelet-derived growth factor-, insulin-like growth factor 1-, and fibroblast growth factor-like molecules. The cytokine production following in vitro exposure, which reflects very early events in the pathogenesis of silicosis, was more strongly related to the high-molecular-weight PDGF-like molecules, whereas the cytokine production following in vivo exposure, which reflects later events in the pathogenesis of silicosis, was more influenced by intermediate-molecular-weight FGF- and IGF-like molecules.

Animals↗
PubMed1994

A mouse model of lung injury induced by microbial products: implication of tumor necrosis factor.

Mice of the C57BL/6 strain were injected with bacterial lipopolysaccharide (LPS) followed by formylnorleucyl-leucyl-phenylalanine (FNLP) by the intraperitoneal route; markers of acute lung injury were examined in mice given a fusion protein of soluble human tumor necrosis factor-alpha (TNF-alpha) receptor (p80) linked to the Fc portion of human IgG (TNFR:Fc) or excipient. Challenge with LPS/FNLP elicited an adult respiratory distress syndrome-like pathology characterized by sharp increases in levels of lactate dehydrogenase (LDH) and total proteins in bronchoalveolar lavage as well as in lung myeloperoxidase (MPO) content at 16 and 20 h after challenge. Infusion of 1 mg of TNFR:Fc 2 h before challenge very significantly abrogated the increases in LDH, protein levels, and MPO. Histologic analysis revealed that LPS/FNLP infusion resulted in an intravascular neutrophil agglomerate and perivascular/peribronchial damage; the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-alpha depletion. There were moderate levels of antigenic TNF-alpha in lung homogenates at 16 and 20 h after challenge, not affected by infusion with TNFR:Fc. No bioactive TNF-alpha was detected in lung homogenates of challenged mice given TNFR:Fc. High levels of antigenic interleukin-6 (IL-6) were found in lung homogenates of challenged mice treated with TNFR:Fc or with diluent. Elevated levels of antigenic IL-6 and TNF-alpha were found in sera of challenged mice at 16 and 20 h after injection; TNFR:Fc-treated mice had a higher level of antigenic TNF-alpha than did challenged mice given diluent, but it was not bioactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Silica-exposed macrophages release a growth-promoting activity for type II pneumocytes.

This study addresses the hypothesis that silica-activated alveolar macrophages could release soluble factors stimulating type II cell proliferation. Macrophages from control sheep were exposed or not in vitro to silica, aluminum-treated silica (Si-Al), or titanium dioxide (TiO2). In addition, macrophages from a model of chromic silica-exposed sheep were studied. Supernatants from unstimulated macrophages were found to double basal type II cell DNA synthesis. Alveolar macrophage-conditioned media (AMCM) collected from cells exposed in vitro to silica induced an additional growth-promoting activity for type II cells. Supernatants from Si-Al- or TiO2 dust-exposed alveolar macrophages had the same effects as unstimulated AMCM. In addition, AMCM from in vivo silicotic sheep cells also contained elevated levels of type II cell mitogenic activity. These results suggest that in vitro as in vivo, silica-activated macrophages produce a type II cell growth factor(s) for type II epithelial cells.

Animals↗
PubMed1993

Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis.

In silicosis, a profile of surfactant overproduction associated with type II epithelial cell hypertrophy and hyperplasia has been documented. In addition, enhanced accumulation of surfactant-associated protein A (SP-A) has been seen in the rat model of acute silicosis by 2 independent groups, but the exact role of these surfactant changes in silicosis are incompletely understood. In this study we measured in lung lavage surfactant total phospholipids and surfactant-associated proteins A and B (SP-A, SP-B). In addition, the surface tension reducing activities of lipid extracts of bronchoalveolar lavage fluids (BALFs) in the sheep silicosis model were examined using a pulsating bubble surfactometer. Two groups of animals (n = 18) were investigated: a saline-exposed (PBS-PBS) group and a silica-exposed (Si-PBS) group. Total surfactant phospholipids in the silicotic sheep increased 2-fold over the control sheep values (p < 0.05), as previously reported. In addition, we found a substantial rise in total surfactant-associated proteins, with significant increase in SP-A (1.16 +/- 0.22 micrograms/ml Si-PBS group vs. 0.70 +/- 0.07 micrograms/ml PBS-PBS group, p < 0.05) and a parallel but not significant increase in SP-B (2.68 +/- 0.90 micrograms/ml Si-PBS group vs. 1.10 +/- 0.30 micrograms/ml PBS-PBS group). The surface-tension-reducing activities of alveolar fluid lipid extracts did not differ significantly between the groups (Si-PBS group at maximal bubble radius [Rmax]: 27.0 +/- 1.6 and at minimal bubble radius [Rmin]: 1.0 +/- 0.7 milli Newton/m, vs. PBS-PBS group Rmax: 27.0 +/- 2.2 and Rmin: 0.7 +/- 0.3 milli Newton/m at 4 min pulsation). The ratios of SP-A and SP-B to lipid phosphorus levels document a proportional enhancement of surfactant-associated proteins and phospholipids, thus suggesting a co-ordinated upregulation of both surfactant-associated proteins and phospholipids in this model of silicosis. However, on an individual basis, these changes were not related, suggesting a more complex model of regulation. This study documents significant increases of the surfactant apoproteins proportional to changes in phospholipids in the lung of silicotic sheep. In spite of these alterations of surfactant components, organic solvent lipid extracts of BAPLFs surfactant remained equally effective in reducing surface tension.

Animals↗
PubMed1993

Phospholipid content of bronchoalveolar lavage fluid in granite workers with silicosis in Quebec.

BACKGROUND: Some of the prominent features of silicosis are hyperplasia and hypertrophy of epithelial type II cells, which in experimental animals are often accompanied by accumulation of phospholipids in the lung. METHODS: The total phospholipid content of lung lavage fluid and its composition in 28 granite stone cutters with long term exposure to silica dust (23 with radiological silicosis) was compared with that of lavage fluid in 15 normal volunteers, 15 patients with untreated idiopathic pulmonary fibrosis, and 19 patients with untreated stage 2 or 3 sarcoidosis. All lavage fluid was obtained at the time of first pulmonary investigation, which also included lung function tests. RESULTS: In the normal subjects total phospholipid content was 1.13 (0.16) micrograms phosphorus/ml of lung lavage, in the patients with idiopathic pulmonary fibrosis 0.52 (0.07) microgram/ml (p < 0.05), and in the patients with sarcoidosis 1.02 (0.20) microgram/ml composition being in the range reported in humans. In the patients with silicosis total phospholipid content was significantly decreased to an average of 0.46 (0.08) microgram/ml compared with the findings in normal subjects and patients with sarcoidosis. Within the group exposed to silica changes in total phospholipid content did not correlate with the severity of the radiographic disease, changes in lung function, the cellularity of lung lavage fluid, or hyaluronate concentrations. The secretory capacity of rat epithelial type II cells was not significantly different when cultured with bronchoalveolar lavage fluid from all four groups of subjects. CONCLUSIONS: Total phospholipid content in lung lavage fluid was significantly reduced in granite workers with radiological evidence of lung disease, but showed no correlation with radiological or functional markers of disease severity.

Adolescent↗
PubMed1993

Farmer's lung. Long-term outcome and lack of predictive value of bronchoalveolar lavage fibrosing factors.

This study evaluates the long-term outcome of farmer's lung (FL), adding high-resolution computed tomograms (HRCT) to previously reported procedures and verifying whether bronchoalveolar lavage (BAL) fluid markers or substrates of fibrosis (hyaluronic acid, Type III procollagen, fibronectin, and fibroblast growth factors) (FF) predict outcome. A total of 33 subjects with a history of FL dating back at least 6 yr were evaluated with pulmonary function tests, chest x-ray (CXR), and HRCT. All subjects had an initial evaluation, which included a BAL, 6 yr before the current study. Subjects were then either in acute FL (n = 19) or in clinical remission despite continued contact (n = 14). In the current study, pulmonary function tests revealed an obstructive profile in 13 subjects, restrictive changes in 1, an isolated decrease in lung diffusion capacity in 3, and normal values in 16. Chest radiographs (CXR) were normal in 22 subjects, abnormal with interstitial or reticulonodular changes in 6, and suggestive of emphysema in 5. HRCT revealed emphysema in 9 subjects; 3 had localized fibrotic changes, 2 a ground-glass pattern, and 19 were normal. There was a good correlation between the findings on pulmonary function tests and HRCT; however, CXR alone did not suggest the existence of emphysema in 4 subjects who had such findings on HRCT. No correlations were found between most outcome parameters and the level of the BAL FF measured 6 yr previously. We conclude that airflow obstruction with or without emphysema is an important long-term sequela of FL and that BAL FF do not predict outcome in this disease.

Acute Disease↗
PubMed1993

Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro.

Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD. When the cationic aminoglycosides, tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited. In addition, tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2. Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides. Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl. In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation. These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation.

Animals↗
PubMed1993

Fibrogenic activities in bronchoalveolar lavage fluid of farmer's lung.

Hyaluronic acid (HA), type III procollagen, fibronectin, and fibroblast growth factors (FGF) were measured in 43 bronchoalveolar lavage fluid (BALF) specimens obtained from 38 patients with farmer's lung (FL) and in BALF of 9 nonexposed normal control subjects. Bronchoalveolar lavage was done in 21 farmers with acute FL (acute) and in 22 with a history of previous FL (Ex) who were still in daily contact with dairy barns. All farmers from the acute and Ex groups had a lymphocytic alveolitis, respectively, 62.7 (3.5) percent (mean [SEM]) and 48.1 (4.3) percent. Hyaluronic acid, type III procollagen, fibronectin, and FGF were all highly increased in acute disease. These substances were also increased in the BALF of subjects of the Ex group who had no clinical symptoms or signs of acute disease at the time of lavage, but were actively farming. The increase in type III procollagen, however, was less in this group than in the subjects with acute disease. These observations suggest that the fibrosing activities and potentialities of the allergic alveolitis of FL are fully expressed at the time of clinical presentation and also in the subclinical phase of the disease in susceptible farmers who remain exposed after an initial acute phase of the disease.

Adult↗