Hypoxia Aggravates Inhibition of Alveolar Epithelial Na-Transport by Lipopolysaccharide-Stimulation of Alveolar Macrophages

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dc.contributor.authorBaloglu, Emel
dc.contributor.authorVelineni, Kalpana
dc.contributor.authorErmis-Kaya, Ezgi
dc.contributor.authorMairbaeurl, Heimo
dc.date.accessioned2023-02-21T12:33:46Z
dc.date.available2023-02-21T12:33:46Z
dc.date.issued2022-01-01
dc.description.abstractInflammation and hypoxia impair alveolar barrier tightness, inhibit Na- and fluid reabsorption, and cause edema. We tested whether stimulated alveolar macrophages affect alveolar Na-transport and whether hypoxia aggravates the effects of inflammation, and tested for involved signaling pathways. Primary rat alveolar type II cells (rA2) were co-cultured with rat alveolar macrophages (NR8383) or treated with NR8383-conditioned media after stimulation with lipopolysaccharide (LPS
dc.description.abstract1 mu g/mL) and exposed to normoxia and hypoxia (1.5\% O-2). LPS caused a fast, transient increase in TNF alpha and IL-6 mRNA in macrophages and a sustained increase in inducible nitric oxide synthase (NOS2) mRNA in macrophages and in rA2 cells resulting in elevated nitrite levels and secretion of TNF-alpha and IL-6 into culture media. In normoxia, 24 h of LPS treated NR8383 decreased the transepithelial electrical resistance (TEER) of co-cultures, of amiloride-sensitive short circuit current (ISC Delta amil)
dc.description.abstractwhereas Na/K-ATPase activity was not affected. Inhibition was also seen with conditioned media from LPS-stimulated NR8383 on rA2, but was less pronounced after dialysis to remove small molecules and nitrite. The effect of LPS-stimulated macrophages on TEER and Na-transport was fully prevented by the iNOS-inhibitor L-NMMA applied to co-cultures and to rA2 mono-cultures. Hypoxia in combination with LPS-stimulated NR8383 totally abolished TEER and ISC Delta amil. These results indicate that the LPS-stimulation of alveolar macrophages impairs alveolar epithelial Na-transport by NO-dependent mechanisms, where part of the NO is produced by rA2 induced by signals from LPS stimulated alveolar macrophages.
dc.description.issue15
dc.description.issueAUG
dc.description.volume23
dc.identifier.doi10.3390/ijms23158315
dc.identifier.urihttps://hdl.handle.net/11443/1579
dc.identifier.urihttp://dx.doi.org/10.3390/ijms23158315
dc.identifier.wosWOS:000839211700001
dc.publisherMDPI
dc.relation.ispartofINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
dc.subjectalveolar epithelial Na-channels
dc.subjectNa/K-ATPase
dc.subjectpulmonary edema
dc.subjectinflammation
dc.subjectiNOS
dc.subjecthypoxia
dc.subjectalveolar macrophages
dc.titleHypoxia Aggravates Inhibition of Alveolar Epithelial Na-Transport by Lipopolysaccharide-Stimulation of Alveolar Macrophages
dc.typeArticle
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