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Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
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2011 (English)In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 5, no 9-10, 513-522 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Respiratory syncytial virus (RSV) is the most common cause of severe respiratory tract infection in infants. The aim was to identify host defence components in nasopharyngeal aspirate (NPA) from infants with RSV infection and to study the expression of the novel 25 kDa innate immunity protein SPLUNC1. less thanbrgreater than less thanbrgreater thanExperimental design: NPAs from infants were analyzed with 2-DE and MS in a pilot study. The levels of SPLUNC1 were analyzed with immunoblotting in 47 NPAs, admitted for RSV diagnosis. less thanbrgreater than less thanbrgreater thanResults: Totally, 35 proteins were identified in NPA, including several innate immunity proteins such as group X phospholipase A(2), different S100 proteins and SPLUNC1. In addition, a new truncated 15 kDa form of SPLUNC1 was identified that was detected in about 50% of the aspirates admitted for RSV diagnosis. RSV-positive boys had significantly less 25 kDa SPLUNC1 than RSV-negative boys while there were no significant differences among girls. less thanbrgreater than less thanbrgreater thanConclusions and clinical relevance: Several important innate immunity proteins were identified in NPA. Notably, a new truncated form of the newly suggested anti-bacterial protein SPLUNC1 was found. It is possible that a decrease in SPLUNC1 in the upper airways may increase the risk for severe pneumonia in boys.

Place, publisher, year, edition, pages
Wiley-VCH Verlag Berlin , 2011. Vol. 5, no 9-10, 513-522 p.
Keyword [en]
MS, Nasopharynx, PLUNC, Respiratory syncytial virus, Two-dimensional gel electrophoresis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-72142DOI: 10.1002/prca.201100016ISI: 000296418400005OAI: oai:DiVA.org:liu-72142DiVA: diva2:457503
Note
Funding Agencies|The Research Council of South East Sweden|FORSS-36761- 8505|Available from: 2011-11-18 Created: 2011-11-18 Last updated: 2015-04-23
In thesis
1. Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents
Open this publication in new window or tab >>Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid.

This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using twodimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health.

Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified.

Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1453
National Category
Environmental Health and Occupational Health Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-117343 (URN)10.3384/diss.diva-117343 (DOI)978-91-7519-129-4 (ISBN)
Public defence
2015-05-21, Hälsans hus, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2015-04-23 Created: 2015-04-23 Last updated: 2015-04-23Bibliographically approved

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Fornander, LouiseGhafouri, BijarKihlström, ErikÅkerlind, BrittTagesson, ChristerLindahl, Mats

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Faculty of Health SciencesWork and Environmental ScienceRehabilitation MedicineOccupational and Environmental Medicine CentrePain and Rehabilitation CentreClinical MicrobiologyDepartment of Clinical MicrobiologyOccupational and Environmental Medicine
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