Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection

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Abstract

Rationale:

Mycoplasma pneumoniaeis a significant cause of pneumonia in humans.

Objectives:

To determine the impact of mycoplasma infection and the host inflammatory response on alveolar type II (ATII) cell ion transportin vivoandin vitro.

Methods:

Mice were infected withM. pulmonisfor measurements of alveolar fluid clearance (AFC)in vivoand isolation of ATII cells. ATII cells were infectedin vivofor determination of epithelial Na+ channel (ENaC) total and cell surface protein levels by biotinylation and Western blot andin vitrofor whole cell patch clamp recording and measurement of nitric oxide (NO) production by chemiluminescence.

Results:

Mycoplasma infection significantly inhibited AFC at 24 h and total and amiloride-sensitive AFC by 48 h postinfection (pi). In contrast, infected myeloperoxidase-deficient mice had similar basal and amiloride-sensitive AFC values to uninfected control mice at 48 h pi. Addition of forskolin restored total and amiloride-sensitive AFC to control values at 48 h pi. ATII cells isolated from infected mice demonstrated normal α, β, and γ ENaC total protein levels; however, infected whole-lung cell-surface levels of γ ENaC were significantly decreased. Patch-clamp recordings demonstrated a significant decrease in total and amiloride-sensitive Na+ currents at 24 h pi. ATII cells demonstrated a significant increase in the production of NO at 24 h pi and inhibition of NO by ATII cells before infection reversed the decrease in total Na+ currents.

Conclusions:

These data indicate that mycoplasma infection results in decreased AFC and functional ENaC via the production of reactive oxygen nitrogen intermediates.

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