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Updated: May 23, 2026
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Estrogen modulation of pneumonia? An immunoglobulin A effect
Abubaker A Ali1, Lawrence N Diebel, David M Liberati
1Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA.
Background:
Laboratory and clinical studies demonstrated a salutary effect of estradiol (E2) on pneumonia and other infectious complications after trauma, while dihydrotestosterone (DHT) failed to show a similar effect. Secretory immunoglobulin A is the principle antibody in the respiratory and other mucosal secretions. Immunoglobulin A (IgA) production and transport into the mucosal secretion is regulated by Toll-like receptor 4 (TLR-4). In addition, E2 may influence immune regulatory cells via TLR-4. We hypothesized that the protective effect of E2 on the development of pneumonia may be related to modulation of IgA transport into respiratory secretions.
Methods:
Calu-3 respiratory epithelial cell monolayers were established in a two-chamber cell culture system. Calu-3 cells were then treated with either E2 or DHT for 3 days for maximal cell stimulation. Dimeric IgA was added to the basal chamber of Calu-3 cells, and IgA transcellular transport was indexed by recovery of secretory immunoglobulin A in the apical chamber media. In separate experiments, Klebsiella pneumonia (10(5) CFU/mL) was added to the apical chamber of treated Calu-3 cell monolayers, and bacterial passage across Calu-3 cells was determined by bacterial recovery from the basal chamber. Calu-3 cells not treated with E2 or DHT served as control.
Results:
Calu-3 cells pretreated with E2 significantly increased IgA transport, and this effect was augmented in a dose-dependent fashion. Only cells pretreated with E2 significantly decreased bacterial passage, and this effect was exhibited in a dose- and time-dependent fashion. E2 led to a significant increase in TLR-4 expression.
Conclusion:
The protective effect of E2 against pneumonia may be related to augmented transport of IgA into the respiratory mucosal secretions.
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