scholarly journals In Vivo Effects of a Synthetic 2-Kilodalton Macrophage-Activating Lipopeptide of Mycoplasma fermentans after Pulmonary Application

2002 ◽  
Vol 70 (7) ◽  
pp. 3785-3792 ◽  
Author(s):  
Anke Lührmann ◽  
Ursula Deiters ◽  
Julia Skokowa ◽  
Michaela Hanke ◽  
Johannes E. Gessner ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lavage Fluid ◽  
Target Cells ◽  
Host Reaction ◽  
Mycoplasma Fermentans ◽  
Monocyte Chemoattractant Protein 1 ◽  
Leukocyte Accumulation ◽  
In Vivo Effects ◽  
Different Doses

ABSTRACT Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans and animals. Mycoplasma infections are characterized by an influx of neutrophils, followed by an accumulation of macrophages and lymphocytes. The present study deals with the question of which mycoplasmal components cause this host reaction. The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar lavage cells were examined at different times after different doses of 2S-MALP-2. Application of 2.5 μg induced a pronounced leukocyte accumulation in the bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2 and 3. Lymphocyte numbers, although amounting to only a few percent of the total bronchoalveolar lavage cells, also increased significantly, with maximal lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count of the lung interstitium was increased on day 3 after treatment. After 10 days all investigated cell populations returned to control levels. Transient chemotactic activity for neutrophils was detected in the bronchoalveolar lavage fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate that mycoplasmal lipoproteins and lipopeptides are probably the most relevant mycoplasmal components for the early host reaction. The primary target cells are likely to be the alveolar macrophages liberating chemokines, which attract further leukocytes.

Increased susceptibility of purinergic receptor-deficient mice to lung infection withPseudomonasaeruginosa

2005 ◽  
Vol 289 (5) ◽  
pp. L890-L895 ◽  
Author(s):  
Cara Geary ◽  
Henry Akinbi ◽  
Tom Korfhagen ◽  
Jean-Etienne Fabre ◽  
Richard Boucher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Purinergic Receptors ◽  
Tissue Injury ◽  
Purinergic Receptor ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Sublethal Dose ◽  
Wild Type ◽  
Double Knockout

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2−/−) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1−/−, or P2Y2−/−, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice ( P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2−/− mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.

Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo

2000 ◽  
Vol 278 (5) ◽  
pp. L914-L922 ◽  
Author(s):  
Toru Arai ◽  
Kin'Ya Abe ◽  
Hiroto Matsuoka ◽  
Mitsuhiro Yoshida ◽  
Masahide Mori ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Mrna Expression ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Type I ◽  
Myeloperoxidase Activity ◽  
Human Lung Fibroblast

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day −3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-α mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-β-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.

scholarly journals Effects of Roflumilast, Selective PDE4 Inhibitor, on Airway Reactivity in Ovalbumin-Sensitized Guinea Pigs

2015 ◽  
Vol 5 (1) ◽  
pp. 12-19
Author(s):  
Nirmathan Tharmalingam ◽  
I. Medvedova ◽  
A. Eichlerova ◽  
M. Prso ◽  
D. Mokra ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Whole Body ◽  
Pde4 Inhibitor ◽  
Airway Reactivity

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.

Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury

2005 ◽  
Vol 289 (5) ◽  
pp. L807-L815 ◽  
Author(s):  
Jörg Reutershan ◽  
Abdul Basit ◽  
Elena V. Galkina ◽  
Klaus Ley
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Transendothelial Migration ◽  
Lavage Fluid ◽  
Pulmonary Vasculature ◽  
Activated Neutrophils ◽  
First Time

Infiltration of activated neutrophils [polymorphonuclear leukocytes (PMN)] into the lung is an important component of the inflammatory response in acute lung injury. The signals required to direct PMN into the different compartments of the lung have not been fully elucidated. In a murine model of LPS-induced lung injury, we investigated the sequential recruitment of PMN into the pulmonary vasculature, lung interstitium, and alveolar space. Mice were exposed to aerosolized LPS and bronchoalveolar lavage fluid (BAL), and lungs were harvested at different time points. We developed a flow cytometry-based technique to assess in vivo trafficking of PMN in the intravascular and extravascular lung compartments. Aerosolized LPS induced consistent PMN migration into all lung compartments. We found that sequestration in the pulmonary vasculature occurred within the first hour. Transendothelial migration into the interstitial space started 1 h after LPS exposure and increased continuously until a plateau was reached between 12 and 24 h. Transepithelial migration into the alveolar air space was delayed, as the first PMN did not appear until 2 h after LPS, reaching a peak at 24 h. Transendothelial migration and transepithelial migration were inhibited by pertussis toxin, indicating involvement of Gαi-coupled receptors. These findings confirm LPS-induced migration of PMN into the lung. For the first time, distinct transmigration steps into the different lung compartments are characterized in vivo.

scholarly journals Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response to Staphylococcus aureus-Induced Pneumonia

2010 ◽  
Vol 78 (3) ◽  
pp. 1353-1363 ◽  
Author(s):  
Antara Banerjee ◽  
Frederik Stevenaert ◽  
Kalyan Pande ◽  
Erik Haghjoo ◽  
Svetlana Antonenko ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILRα and activating PILRβ are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb −/− mice or mice in which PILRα was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 and elevated levels of gamma interferon (IFN-γ), IL-12, and IL-10. In contrast, mice in which PILRβ was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1β, TNF-α, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1α in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb −/− mice released significantly less IL-1β and TNF-α and more IFN-γ and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILRβ. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILRα or deletion of PILRβ, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation.

Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung

2004 ◽  
Vol 286 (3) ◽  
pp. L488-L493 ◽  
Author(s):  
Michael A. Vozzelli ◽  
S. Nicholas Mason ◽  
Mary H. Whorton ◽  
Richard L. Auten
Keyword(s):  
Inflammatory Response ◽  
Bronchoalveolar Lavage ◽  
Protein Oxidation ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Cells ◽  
Newborn Rats ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cellular Inflammatory Response

Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O2or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3–5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O2-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.

scholarly journals Sevoflurane Ameliorates Gas Exchange and Attenuates Lung Damage in Experimental Lipopolysaccharide-induced Lung Injury

2009 ◽  
Vol 111 (6) ◽  
pp. 1238-1248 ◽  
Author(s):  
Stefanie Voigtsberger ◽  
Robert A. Lachmann ◽  
Anik C. Leutert ◽  
Martin Schläpfer ◽  
Christa Booy ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Messenger Rna ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Total Cell ◽  
Lung Damage ◽  
In Vivo Model ◽  
Albumin Content

Background Acute lung injury is a common complication in critically ill patients. Several studies suggest that volatile anesthetics have immunomodulating effects. The aim of the current study was to assess possible postconditioning with sevoflurane in an in vivo model of endotoxin-induced lung injury. Methods Rats were anesthetized, tracheotomized, and mechanically ventilated. Lipopolysaccharide (saline as control) was administered intratracheally. Upon injury after 2 h of propofol anesthesia, general anesthesia was continued with either sevoflurane or propofol for 4 h. Arterial blood gases were measured every 2 h. After 6 h of injury, bronchoalveolar lavage was performed and lungs were collected. Total cell count, albumin content, concentrations of the cytokines cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1, and phospholipids were analyzed in bronchoalveolar lavage fluid. Expression of messenger RNA for the two cytokines and for surfactant protein B was determined in lung tissue. Histopathologic examination of the lung was performed. Results Significant improvement of the ratio of oxygen tension to inspired oxygen fraction was shown with sevoflurane (mean + or - SD: 243 + or - 94 mmHg [32.4 kPa]) compared with propofol (88 + or - 19 mmHg [11.7 kPa]). Total cell count representing effector cell recruitment as well as albumin content as a measure of lung permeability were significantly decreased in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group in bronchoalveolar lavage fluid. Expression of the cytokines protein in bronchoalveolar lavage fluid as well as messenger RNA in lung tissue was significantly lower in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group. Conclusions Postconditioning with sevoflurane attenuates lung damage and preserves lung function in an in vivo model of acute lung injury.

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