S47 Pneumolysin promotes neutrophil: platelet aggregation in vitro (original) (raw)
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Jolliet, Bulpa, Thorens, Ritz, Chevrolet vasodilator responsiveness in primary pulmonary hyper-with mixed connective tissue disease. Thorax 1995;50: 96-7. tension. Circulation 1990;82:2018-26. 9 Weir EK, Rubin LJ, Ayres SM, Bergofsky EH, Brundage 4 Sitbon O, Brenot F, Denjean A, Bergeron A, Parent F, BH, Detre KM, et al. The acute administration of vaso-Azarian R, et al. Inhaled nitric oxide as a screening vasodilators in primary pulmonary hypertension. Am Rev Respir dilator agent in primary pulmonary hypertension. Am J Semigran MJ. Response to inhaled nitric oxide identifies 11 Rich S, Brundage B. High-dose calcium channel-blocking a subset of patients with pulmonary hypertension likely therapy for primary pulmonary hypertension: evidence for to respond to high dose calcium channel antagonists. Am long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation J Respir Crit Care Med 1995;151:A728. 1987;76:135-41. 6 Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage 12 Jones DK, Higenbottam TW, Wallwork J. Treatment of BH, et al. Primary pulmonary hypertension: a national primary pulmonary hypertension with intravenous epoprospective study. Ann Intern Med 1987;107:216-23. prostenol. Br Heart J 1987;57:270-8. 7 Chevrolet JC, Schmid F. "Spontaneous" variability of pul-13 Sprague RS, Stephenson AH, Lonigro AJ. Prostaglandin I 2 monary haemodynamics during vasodilator tests in pulsupports blood flow to hypoxic alveoli in anesthetized monary precapillary hypertension. Eur J Intern Med 1992; dogs. J Appl Physiol 1984;56:1246-51. 3:305-17. 14 Lynch JP, Myhre JG, Dantzker DR. Influence of cardiac 8 Jolliet P, Thorens JB, Chevrolet JC. Pulmonary vascular output on intrapulmonary shunt. J Appl Physiol 1979;46: 315-21. reactivity in severe pulmonary hypertension associated Thorax 1997;52:372-374
The American Journal of Pathology, 2010
Vascular endothelial growth factor-A (VEGF) is a potent regulator of vascular permeability, inflammatory response, and cell survival in the lung. To explore the functions of VEGF produced locally in type II pneumocytes, we generated mice with a conditional deletion of VEGF-A using Cre recombinase driven by the human surfactant protein C (SPC) promoter. In 7to 10-week-old VEGF-knockout (SPC-VEGF-KO) mice, lung histology and physiology were essentially normal, except for higher dynamic lung compliance and lower pulmonary vascular permeability. Emphysema was seen in 28-to 32-week-old animals. To investigate the role of type II pneumocyte-derived VEGF in acute lung injury, we challenged 7-to 10-week-old SPC-VEGF-KO mice and their wild-type littermates with intestinal ischemia-reperfusion. Bronchoalveolar lavage fluid total cell count, pulmonary permeability, and lung injury score were significantly attenuated, and total lung VEGF levels were significantly lower in SPC-VEGF-KO mice compared with wild-type controls. In SPC-VEGF-KO mice, activated caspase 3-positive type II epithelial cells were increased after intestinal ischemia-reperfusion, even though there was no significant difference in the total number of cells positive for terminal deoxynucleotidyl transferase dUTP nick-end labeling. We conclude that VEGF in type II cells helps protect alveolar epithelial cells from caspase-dependent apoptosis. However, VEGF produced from type II cells may contribute to increased vascular permeability during acute lung injury. (Am J
Macrophages, neutrophils and tumour necrosis factor- α expression in bronchiectatic airways in vivo
Respiratory Medicine, 2001
Bronchiectasis is increasingly being recognized as an in£ammatory condition of the airways in which pathological permanent dilation occurs.We have obtained endobronchial biopsies in14 patients with stable bronchiectasis and 15 control subjects. Airway neutrophils, macrophages and tumour necrosis factor-a (TNFa)-positive cells were stained with monoclonal antibodies and the densities of positive cells in the lamina propria were determined by using a computer image analyser.There was signi¢cantly higher neutrophil, macrophage and TNFa-positive cell densitiesin the lamina propria of bronchiectatic than control airways (P50?001, P50?001and P=0?0002, respectively). Airway neutrophil density, in bronchiectasis but not in controls, correlated withTNFa-positive cell density (r=0?71, P=0?004). A signi¢cant correlation between airway macrophage and TNFa-positive cell densities was demonstrated in both control and bronchiectatic airways (r=0?63, P=0?016 and r=0?60, P=0?02 respectively).Neutrophil density negatively correlated with per cent forced vital capacity (FVC%) predicted among patients with bronchiectasis (r=70?53, P=0?04). Bronchiectasis patients who were regular sputum producers had a signi¢cantly higher macrophage, but not neutrophil density, than their counterparts (P=0?02 and P=0?48 respectively). Our original ¢ndings suggest that airway macrophages could contribute to neutrophil in£ux into airway walls through their production of TNFa and therefore play an important role in the pathogenesis of bronchiectasis.
Dual Role of Vascular Endothelial Growth Factor in Experimental Obliterative Bronchiolitis
American Journal of Respiratory and Critical Care Medicine, 2005
Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. We investigated the role of vascular endothelial growth factor (VEGF) in the development of OB in rat tracheal allografts. In nonimmunosuppressed allografts, VEGF mRNA and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells with progressive loss of epithelium and airway occlusion compared to syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF 164 gene increased early epithelial cell proliferation and regeneration but increased microvascular remodeling and lymphangiogenesis, and luminal occlusion by more than 50% compared to AdlacZ-treated allografts. Although VEGFR inhibition decreased early epithelial regeneration in non-infected allografts, it reduced microvascular remodeling, lymphangiogenesis, intragraft traffic of CD4 + and CD8 + T cells, and the degree of luminal occlusion. Simultaneous VEGF gene transfer and PDGFR inhibition with imatinib preserved respiratory epithelium and totally prevented luminal occlusion. In conclusion, our findings indicate that VEGF has a dual role in transplant OB. Our results suggest that VEGF may protect epithelial integrity. On the other hand, VEGF may enhance luminal occlusion by increasing the recruitment of mononuclear inflammatory cells with PDGF acting as a final effector molecule in this process.
Angiogenesis and Remodeling of Airway Vasculature in Chronic Inflammation
American Journal of Respiratory and Critical Care Medicine, 2001
Angiogenesis and microvascular remodeling are known features of chronic inflammatory diseases such as asthma and chronic bronchitis, but the mechanisms and consequences of the changes are just beginning to be elucidated. In a model of chronic airway inflammation produced by Mycoplasma pulmonis infection of the airways of mice or rats, angiogenesis and microvascular remodeling create vessels that mediate leukocyte influx and leak plasma proteins into the airway mucosa. These vascular changes are driven by the immune response to the organisms. Plasma leakage results from gaps between endothelial cells, as well as from increased vascular surface area and probably other changes in the newly formed and remodeled blood vessels. Treatment with long-acting  2 agonists can reduce but not eliminate the plasma occurring after infection. In addition to the elevated baseline leakage, the remodeled vessels in the airway mucosa are abnormally sensitive to substance P, but not to platelet-activating factor or serotonin, suggesting that the infection leads to a selective upregulation of NK1 receptors on the vasculature. The formation of new vessels and the remodeling of existing vessels are likely to be induced by multiple growth factors, including vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). VEGF increases vascular permeability, but Ang1 has the opposite effect. This feature is consistent with evidence that VEGF and Ang1 play complementary and coordinated roles in vascular growth and remodeling and have powerful effects on vascular function. Regulation of vascular permeability by VEGF and Ang1 may be their most rapid and potent actions in the adult, as these effects can occur independent of their effects on angiogenesis and vascular remodeling. The ability of Ang1 to block plasma leakage without producing angiogenesis may be therapeutically advantageous. Furthermore, because VEGF and Ang1 have additive effects in promoting angiogenesis but opposite effects on vascular permeability, they could be used together to avoid the formation of leaky vessels in therapeutic angiogenesis. Finally, the elucidation of the protective effect of Ang1 on blood vessel leakiness to plasma proteins raises the possibility of a new strategy for reducing airway edema in inflammatory airway diseases such as asthma and chronic bronchitis.
Induced sputum and bronchoalveolar lavage from patients with hypersensitivity pneumonitis
Respiratory Medicine, 2004
Background and Aim: Hypersensitivity pneumonitis (HP) is an immunologically induced inflammation of the lung parenchyma, though bronchial airways may be also involved. The aim of this study was to compare the cellular profiles of induced sputum (IS) in patients with newly diagnosed HP to that of healthy subjects, and to examine the relationship between inflammatory cells from IS and BAL.
Association Between Bronchiectasis, Systemic Inflammation, and Tumor Necrosis Factor
Archivos De Bronconeumologia, 2008
The relationship between systemic inflammation and different measures of bronchiectasis severity has not been described. The objective of this study was to analyze the relationship between plasma concentrations of tumor necrosis factorα (TNF-α), as a marker of systemic inflammation, and some commonly used criteria for quantifying bronchiectasis severity in clinically stable patients whose disease was not caused by cystic fibrosis.Sixty-eight clinically stable patients with bronchiectasis and 19 age- and sex-matched healthy control subjects were included in the study. Data on disease history, symptoms, severity, functional variables, sputum volume, and microbiological cultures, laboratory findings, and other indicators of disease course were collected. Plasma concentrations of TNF-α were measured using high-resolution enzyme-linked immunosorbent assay.Plasma concentrations of TNF-α were higher in patients than controls (8.28 vs 5.67 pg/mL; P=.001). This observation correlated with other markers of systemic inflammation such as erythrocyte sedimentation rate (r=0.42; P=.001), C-reactive protein (r=0.45; P=.001), and percentage of peripheral blood neutrophils (r=0.45; P=.001). Patients with high plasma concentrations of TNF-α (>8.1 pg/dL) had more severe disease (5.19 vs 3.21; P=.001), were more likely to have respiratory failure (37.5% vs 8.3%; P=.003), and a higher rate of Pseudomonas aeruginosa colonization (34.3% vs 8.3%; P=.008).High plasma concentrations of TNF-α were associated with several criteria usually used to assess severity of bronchiectasis in clinically stable patients with disease not caused by cystic fibrosis.La relación existente entre la presencia de inflamación sistémica y los diferentes parámetros de gravedad en pacientes con bronquiectasias no ha sido descrita. El objetivo del estudio ha sido analizar la relación entre las concentraciones plasmáticas de factor de necrosis tumoral alfa (pTNF-α), como marcador de inflamación sistémica, y algunos criterios de gravedad comúnmente utilizados en pacientes con bronquiectasias, en fase de estabilidad clínica, no debidas a fibrosis quística.Se incluyó en el estudio a 68 pacientes con bronquiectasias clínicamente estables y 19 controles sanos ajustados según edad y sexo. Se recogieron datos referentes a antecedentes patológicos, síntomas, extensión, variables funcionales, volumen de esputo y aspectos micro-biológicos, analíticos y evolutivos. Las concentraciones de pTNF-α se analizaron utilizando un método de enzimoinmunoanálisis de alta resolución.Se observó una mayor concentración de pTNF-α en los pacientes que en los controles (8,28 frente a 5,67 pg/ml; p = 0,001), que se correlacionó con otros parámetros de inflamación sistémica como la velocidad de sedimentación globular (r = 0,42; p = 0,001), la proteína C reactiva (r = 0,45; p = 0,001) y el porcentaje de neutrófilos periféricos (r = 0,45; p = 0,001). Los pacientes con concentraciones elevadas de pTNF-α (> 8,1 pg/dl) presentaron mayor extensión de la enfermedad (5,19 frente a 3,21; p = 0,001), mayor probabilidad de presentar insuficiencia respiratoria (el 37,5 frente al 8,3%; p = 0,003) y mayor porcentaje de colonizaciones por Pseudomonas aeruginosa (el 34,3 frente al 8,3%; p = 0,008).Las concentraciones elevadas de pTNF-α se asocian a varios parámetros comúnmente utilizados para valorar la gravedad en pacientes con bronquiectasias clínicamente estables y no debidas a fibrosis quística.