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Molecular analysis of serum and bronchoalveolar lavage in a mouse model of
influenza reveals markers of disease severity that can be clinically useful in
humans
#MMPMID24505273
Kumar Y
; Liang C
; Limmon GV
; Liang L
; Engelward BP
; Ooi EE
; Chen J
; Tannenbaum SR
PLoS One
2014[]; 9
(2
): e86912
PMID24505273
show ga
BACKGROUND: Management of influenza, a major contributor to the worldwide disease
burden, is complicated by lack of reliable methods for early identification of
susceptible individuals. Identification of molecular markers that can augment
existing diagnostic tools for prediction of severity can be expected to greatly
improve disease management capabilities. METHODOLOGY/PRINCIPAL FINDINGS: We have
analyzed cytokines, proteome flux and protein adducts in bronchoalveolar lavage
(BAL) and sera from mice infected with influenza A virus (PR8 strain) using a
previously established non-lethal model of influenza infection. Through detailed
cytokine and protein adduct measurements of murine BAL, we first established the
temporal profile of innate and adaptive responses as well as macrophage and
neutrophil activities in response to influenza infection. A similar analysis was
also performed with sera from a longitudinal cohort of influenza patients. We
then used an iTRAQ-based, comparative serum proteome analysis to catalog the
proteome flux in the murine BAL during the stages correlating with "peak
viremia," "inflammatory damage," as well as the "recovery phase." In addition to
activation of acute phase responses, a distinct class of lung proteins including
surfactant proteins was found to be depleted from the BAL coincident with their
"appearance" in the serum, presumably due to leakage of the protein following
loss of the integrity of the lung/epithelial barrier. Serum levels of at least
two of these proteins were elevated in influenza patients during the febrile
phase of infection compared to healthy controls or to the same patients at
convalescence. CONCLUSIONS/SIGNIFICANCE: The findings from this study provide a
molecular description of disease progression in a mouse model of influenza and
demonstrate its potential for translation into a novel class of markers for
measurement of acute lung injury and improved case management.
|*Bronchoalveolar Lavage Fluid
[MESH]
|Acute Lung Injury/metabolism/pathology
[MESH]
|Animals
[MESH]
|Biomarkers/metabolism
[MESH]
|Cytokines/*metabolism
[MESH]
|Disease Models, Animal
[MESH]
|Humans
[MESH]
|Influenza A Virus, H1N1 Subtype/*metabolism
[MESH]
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