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Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Arbets- och miljövetenskap.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin. Östergötlands Läns Landsting, Sinnescentrum, Smärt och rehabiliteringscentrum.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
Vise andre og tillknytning
2011 (engelsk)Inngår i: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 5, nr 9-10, s. 513-522Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Wiley-VCH Verlag Berlin , 2011. Vol. 5, nr 9-10, s. 513-522
Emneord [en]
MS, Nasopharynx, PLUNC, Respiratory syncytial virus, Two-dimensional gel electrophoresis
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-72142DOI: 10.1002/prca.201100016ISI: 000296418400005OAI: oai:DiVA.org:liu-72142DiVA, id: diva2:457503
Merknad
Funding Agencies|The Research Council of South East Sweden|FORSS-36761- 8505|Tilgjengelig fra: 2011-11-18 Laget: 2011-11-18 Sist oppdatert: 2015-04-23
Inngår i avhandling
1. Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents
Åpne denne publikasjonen i ny fane eller vindu >>Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2015. s. 72
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1453
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-117343 (URN)10.3384/diss.diva-117343 (DOI)978-91-7519-129-4 (ISBN)
Disputas
2015-05-21, Hälsans hus, Campus US, Linköping, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2015-04-23 Laget: 2015-04-23 Sist oppdatert: 2019-11-15bibliografisk kontrollert

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