TY - GEN
T1 - Lung basement membranes are compositionally and structurally altered following resolution of acute inflammation.
AU - Brand, Oliver
AU - Kirkham, Sara
AU - Jagger, Christopher
AU - Ozols, Matiss
AU - Lennon, Rachel
AU - Hussell, Tracy
AU - Eckersley, Alexander
PY - 2024/8/19
Y1 - 2024/8/19
N2 - Identification of pathways preventing recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected persistent reduction in lung basement membrane proteins in mice recovered from influenza infection. Basement membrane provides a critical scaffold for heterogeneous cell types and the proteins they secrete/express at the endothelial and epithelial barrier. Further peptide location fingerprinting analysis shows inherent structure-associated changes within core collagen IV and laminin components, particularly within matrikine-producing regions of collagen IV. Our results imply lingering damage to the basement membrane network despite full recovery from viral infection. Surprisingly, these structure-associated changes in laminin and collagen IV components are also observed in non-infected aged mice indicating that inflammation-driven basement membrane degeneration may contribute to tissue ageing. Interestingly, macrophages in regions deficient in basement membrane express collagen IV and laminin chains. Repair of the basement membrane should therefore be targeted to improve overall lung health.
AB - Identification of pathways preventing recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected persistent reduction in lung basement membrane proteins in mice recovered from influenza infection. Basement membrane provides a critical scaffold for heterogeneous cell types and the proteins they secrete/express at the endothelial and epithelial barrier. Further peptide location fingerprinting analysis shows inherent structure-associated changes within core collagen IV and laminin components, particularly within matrikine-producing regions of collagen IV. Our results imply lingering damage to the basement membrane network despite full recovery from viral infection. Surprisingly, these structure-associated changes in laminin and collagen IV components are also observed in non-infected aged mice indicating that inflammation-driven basement membrane degeneration may contribute to tissue ageing. Interestingly, macrophages in regions deficient in basement membrane express collagen IV and laminin chains. Repair of the basement membrane should therefore be targeted to improve overall lung health.
UR - https://doi.org/10.1101/2024.08.19.608567
U2 - 10.1101/2024.08.19.608567
DO - 10.1101/2024.08.19.608567
M3 - Other contribution
PB - bioRxiv
ER -