Neutrophils induce damage to respiratory epithelial cells infected with respiratory syncytial virus

Wang, S Z; Xu, Huji; Wraith, A; Bowden, Jeffrey; Alpers, J. H.; Forsyth, Kevin

doi:10.1183/09031936.98.12030612

Cited by 86 publications

(88 citation statements)

References 28 publications

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“…It has been reported that RSV infection of respiratory epithelial monolayers can promote neutrophil adherence which could, in turn, potentially contribute to the airway injury and obstruction that accompanies bronchiolitis [9]. Our recent studies show that neutrophils augment the damage to respiratory epithelial cells induced by RSV infection in vitro [10]. The modulation of neutrophil apoptosis in RSV infection in vivo may regulate the epithelial damage induced by neutrophils.…”

Section: Introductionmentioning

confidence: 76%

“…The accelerated neutrophil apoptotic process in vivo may limit the release of neutrophil contents from disintegrating cells in the airways in RSV bronchiolitis [8] and prevent further injuries to the epithelial cells induced by neutrophils in RSV infection [4,10]. On the other hand, because apoptotic neutrophils are functionally impaired [32], accelerated neutrophil apoptosis in vivo may contribute to the risk of secondary infection [11], which has been associated with RSV infection [33,34].…”

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confidence: 99%

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The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

Wang

Smith

Lovejoy

et al. 1998

Clinical and Experimental Immunology

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SUMMARYNeutrophils are the predominant inflammatory cell in the lung tissues and airways in RSV infection, and can augment the epithelial cell damage induced by RSV. Neutrophil apoptosis has been suggested to be a mechanism to reduce the potential for tissue injury. The apoptosis of neutrophils from nasopharyngeal aspirates (NPA) (n ¼ 19) and peripheral blood (PB) of infants with RSV bronchiolitis (n ¼ 11) and PB from healthy controls (n ¼ 9) was investigated. Monoclonal antibody against CD95 (Fas) and a binding protein Annexin V were used to determine the apoptosis of neutrophils. The expression of CD11b and CD18 on neutrophils was also detected with flow cytometry. The mean fluorescence intensity (MFI) of CD95 on neutrophils from RSV þ NPA was increased compared with cells from control PB (73·6 Ϯ 7·6 versus 31·5 Ϯ 4·3); the MFI of Annexin V, CD11b and CD18 on neutrophils from RSV þ NPA was upregulated compared with cells from both control PB (105·3 Ϯ 18·1 versus 11·8 Ϯ 1·5; 1683 Ϯ 153·3 versus 841·1 Ϯ 72·3; 517 Ϯ 50·5 versus 147 Ϯ 8·7, respectively) and RSV þ PB (105·3 Ϯ 18·1 versus 35·8 Ϯ 4·1; 1683 Ϯ 153·3 versus 818 Ϯ 141·2; 517 Ϯ 50·5 versus 260 Ϯ 25·8, respectively). Furthermore, the percentage of neutrophils expressing Annexin V and the MFI of CD18 on neutrophils from RSV þ PB were increased compared with neutrophils from control PB. In addition, both CD11b (MFI) and CD18 (MFI) correlated with Annexin V (MFI) on neutrophils. We conclude that neutrophil apoptosis in RSV bronchiolitis is accelerated; and CD11b/CD18 may play an important role in RSV infection by influencing neutrophil apoptosis.

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Section: Introductionmentioning

confidence: 76%

mentioning

confidence: 99%

The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

Wang

Smith

Lovejoy

et al. 1998

Clinical and Experimental Immunology

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“…Leukocyte populations of the connecting airway in severe RSV infection are typically composed of neutrophils, and they participate in the viral immunopathology [34]. Epithelial sloughing and necrosis is, in part, a direct result of neutrophil adhesion and exocytosis [35]. RSV infection of epithelial cells and monocytes leads to a synergistic up-regulation in expression of interleukin-8 (IL-8), a CXC chemokine that enhances neutrophilic chemotaxis, and enhanced IL-8 expression is correlated with severe RSV infection [36,37].…”

Section: Discussionmentioning

confidence: 99%

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model

Meyerholz

Grubor

Fach

et al. 2004

Microbes and Infection

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Respiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that perinatal RSV clearance is age-dependent, which may explain the severity of RSV infection in preterm infants. The preterm lamb model is useful for assessing agedependent mechanisms of severe RSV infection. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AbstractRespiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that peri...

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“…Furthermore, a neutrophil-rich exudate detected by bronchoalveolar lavage has been described (13). These polymorphonuclear neutrophil granulocytes (PMN) adhere to the RSV-infected epithelial cells and become activated thereby (14,15). As a consequence, they release reactive oxygen radicals and hydrolytic enzymes and, therefore, are responsible primarily for the subsequent intense inflammation of the lung (16,17).…”

Section: And Wolfgang Königmentioning

confidence: 99%

“…For the synthesis of cDNA, prepared total RNA (2 g) was mixed with Moloney murine leukemia virus reverse transcriptase buffer (3 mM MgCl 2 , 75 mM KCl, 50 mM Tris-HCl; Life Technologies), 0.5 mM deoxyribonucleoside triphosphates (dNTP-Set; Life Technologies), 1 U/ l RNase inhibitor (Amersham), 4 U/ l Moloney murine leukemia virus reverse transcriptase (Life Technologies), and 2.0 ng of oligo(dT) [12][13][14][15][16][17][18] in a volume of 50 l. The synthesis of cDNA was done by heating at 37°C for 60 min. The cDNA was stored at Ϫ20°C.…”

Section: Rt-pcr Analysis Of Icam-1mentioning

confidence: 99%

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

Arnold

König

2005

The Journal of Immunology

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Respiratory syncytial virus (RSV) is worldwide the most frequent cause of bronchiolitis and pneumonia in infants requiring hospitalization. In the present study, we supply evidence that human lung microvascular endothelial cells, human pulmonary lung aorta endothelial cells, and HUVEC are target cells for productive RSV infection. All three RSV-infected endothelial cell types showed an enhanced cell surface expression of ICAM-1 (CD54), which increased in a time- and RSV-dose-dependent manner. By using noninfectious RSV particles we verified that replication of RSV is a prerequisite for the increase of ICAM-1 cell surface expression. The up-regulated ICAM-1 expression pattern correlated with an increased cellular ICAM-1 mRNA amount. In contrast to ICAM-1, a de novo expression of VCAM-1 (CD106) was only observed on RSV-infected HUVEC. Neither P-selectin (CD62P) nor E-selectin (CD62E) was up-regulated by RSV on human endothelial cells. Additional experiments performed with neutralizing Abs specific for IL-1α, IL-1β, IL-6, and TNF-α, respectively, excluded an autocrine mechanism responsible for the observed ICAM-1 up-regulation. The virus-induced ICAM-1 up-regulation was dependent on protein kinase C and A, PI3K, and p38 MAPK activity. Adhesion experiments using polymorphonuclear neutrophil granulocytes (PMN) verified an increased ICAM-1-dependent adhesion rate of PMN cocultured with RSV-infected endothelial cells. Furthermore, the increased adhesiveness resulted in an enhanced transmigration rate of PMN. Our in vitro data suggest that human lung endothelial cells are target cells for RSV infection and that ICAM-1 up-regulated on RSV-infected endothelial cells might contribute to the enhanced accumulation of PMN into the bronchoalveolar space.

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Neutrophils induce damage to respiratory epithelial cells infected with respiratory syncytial virus

Cited by 86 publications

References 28 publications

The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

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