Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome

Tang, Nelson L.S.; Chan, Paul K.S.; Wong, Chun Kwok; To, Ka Fai; Wu, Alan; Sung, Ying Man; Hui, David S.; Sung, Joseph J.; Lam, Christopher Wai Kei

doi:10.1373/clinchem.2005.054460

Cited by 210 publications

(202 citation statements)

References 33 publications

(45 reference statements)

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…However, culturing and infecting the type II cell at an air-liquid interface (A/L) allowed for significant infection and characterization of their innate immune response. The robust innate immune response of these cells to SARS-CoV infection consisted of marked elevations in mRNA concentrations of interferon-b, interferon-l, CXCL10, CXCL11, and IL-6, and these results mirror findings reported in the lungs and sera of patients with SARS (22,23,25).…”

Section: Clinical Relevancesupporting

confidence: 74%

“…Concentrations of multiple proinflammatory cytokines and chemokines have been reported to be increased in the lungs and sera of patients with SARS (22,23,25,26). Because alveolar type II cells at the A/L were readily infected by SARS-CoV, we were able to measure changes in expression of selected genes of the innate immune system in these cells in response to SARS-CoV infection ( Figure 5).…”

Section: Alveolar Type II Cell Cultures At the A/l Display A Vigorousmentioning

confidence: 99%

“…During the course of SARS-CoV infection, a marked elevation was evident in serum concentrations of proinflammatory cytokines, including CXCL10 (IP-10), CCL2 (MCP-1), IL-6, and CXCL8 (IL-8) (1,(22)(23)(24)(25)(26). However, it remains unknown whether these serum cytokines were produced by epithelial cells …”

mentioning

confidence: 99%

See 2 more Smart Citations

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Qian

Travanty

Oko

et al. 2013

Am J Respir Cell Mol Biol

286

266

View full text Add to dashboard Cite

Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an airliquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-b and interferon-l (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.Keywords: lung innate immune response; cytokine responses to SARS coronavirus; lung cell differentiation; air-liquid interface culturesSevere acute respiratory syndrome-associated coronavirus (SARSCoV) produces devastating viral pneumonia (1, 2). Pathologic changes are most prominent in the lungs, with disruptions of the epithelium in gas exchange areas and conducting airways (2-4). The epithelial cells of the alveoli and the conducting airways are the primary targets of SARS-CoV in the human lung, and they express the SARS receptor, angiotension-converting enzyme-2 (ACE2) (5-8). In autopsies of patients with SARS, coronavirus RNA and proteins have been detected in type II cells via immunocytochemisty and in situ hybridization (7,(9)(10)(11)(12)(13)(14). In the aged macaque model of SARS, in which the initial site of infection in the lung can be studied, virus infection was detected in both alveolar type I and type II cells (11,15). In human SARS autopsy specimens, the infection of alveolar macrophages was also suggested because they contained SARS antigens and formed multinucleated giant cells (2, 11). However, in vitro human alveolar macrophages, monocyte-derived dendritic cells, and monocytes are not readily susceptible to SARS-CoV, and these cell types show only very modest cytokine and interferon responses upon exposure to SARS-CoV (16-21).One of the major...

show abstract

Section: Clinical Relevancesupporting

confidence: 74%

Section: Alveolar Type II Cell Cultures At the A/l Display A Vigorousmentioning

confidence: 99%

See 1 more Smart Citation

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Qian

Travanty

Oko

et al. 2013

Am J Respir Cell Mol Biol

286

266

View full text Add to dashboard Cite

show abstract

“…Recently accumulated evidence has demonstrated an elevated serum IP-10 level in various diseases, including inflammatory disease, and has shown its utility as a clinically useful biomarker. [13][14][15] For instance, Tang et al 16 demonstrated that IP-10 is an independent predictor of outcome for severe acute respiratory syndrome patients. Another group has demonstrated elevated IP-10 levels in patients with coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of the Th1 chemoattractant interferon-gamma-inducible protein (IP) 10 are elevated in patients with essential hypertension

Stumpf

Auer

Yılmaz³

et al. 2011

Hypertens Res

View full text Add to dashboard Cite

Growing evidence shows that inflammation has a pivotal role in the pathophysiology of essential hypertension (EH). Although it has been acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages, but T lymphocytes have recently become the center of interest. The goal of our study was to evaluate the role of T-cell-specific cytokines in the pathogenesis of EH. The study examined 39 patients with EH (57.7±6.8 years, systolic blood pressure (SBP) 157.5 ± 11.8 mm Hg, diastolic blood pressure 92.2 ± 12.9 mm Hg, mean arterial pressure 113.9 ± 12.6 mm Hg) and 30 healthy, normotensive controls (55.2 ± 4.9 years). Blood was drawn from a peripheral vein, and serum levels of interferon-inducible protein (IP)-10 and interleukins (IL)-4, -7 and -13 were measured by a multiplexing assay. Hypertensive patients had significantly higher levels of IP-10, IL-4, IL-7 and IL-13 than control subjects. When the patients were classified into tertiles according to their serum IP-10 levels (T1: 41.2-94.1 pg ml À1 ; T2: 103.4-162.5 pg ml À1 ; T3: 171.7-443.5 pg ml À1 ), the patients classified into the highest tertile also had the highest blood pressure. In a correlation analysis, plasma IP-10 concentration was significantly associated with SBP (r¼0.59, Po0.001). Furthermore, hypertensives with microalbuminuria, an early sign of hypertensive target organ damage, had the highest IP-10 levels. A stepwise multivariate regression analysis revealed IP-10 as the strongest independent predictor of SBP (P¼0.01). In conclusion, our study provides new insights into the pathophysiological mechanisms in EH linking inflammation and IP-10. However, these preliminary results need to be confirmed in larger trials.

show abstract

“…In case of coronavirus infection, either MERS-CoV or SARSCoV, it was observed that virus infection induces an excessive activation of the immune system which leads to the synthesis of several pro-inflammatory cytokines like interleukin-1beta (IL-1B), IL-6, IL-8, CXC-chemokine ligand 10 (CXCL10), CC-chemokine ligand 2 (CCL2), and interferon-γ (IFN-γ) [9][10][11][12]. This proinflammatory response will ultimately induce pulmonary circulation capillary leakage which will lead to non-cardiogenic pulmonary edema, hypoxemia, type II pneumocyte hyperplasia, and neutrophil infiltration.…”

mentioning

confidence: 99%

Severe viral pneumonia in adults: what is important for the ICU physician?

Gattarello

Rello

2017

Hospital Practice

View full text Add to dashboard Cite

Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome

Abstract: Increased plasma IP-10 during the first week of SARS symptoms is an independent predictor of outcome. Chemokine activation may be an early event in SARS, and an exaggerated host response may produce complications.

Cited by 210 publications

References 33 publications

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Serum levels of the Th1 chemoattractant interferon-gamma-inducible protein (IP) 10 are elevated in patients with essential hypertension

Severe viral pneumonia in adults: what is important for the ICU physician?

Contact Info

Product

Resources

About