CFTR in alveolar type 1 cells contributes to lung liquid secretion and host defense
Sayahi Suthakaran, Sonya Homami, Deebly Chavez, Stephanie Tang, Sarah K.L. Moore, Chaya Sussman, Jimmy Zhang, Clemente J. Britto, Alice Prince, Alison J. May, Jaymin J. Kathiriya, Jaime L. Hook
Sayahi Suthakaran, Sonya Homami, Deebly Chavez, Stephanie Tang, Sarah K.L. Moore, Chaya Sussman, Jimmy Zhang, Clemente J. Britto, Alice Prince, Alison J. May, Jaymin J. Kathiriya, Jaime L. Hook
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Research Article Cell biology Infectious disease Pulmonology

CFTR in alveolar type 1 cells contributes to lung liquid secretion and host defense

Abstract

CFTR in the lung epithelium contributes to the secretion of a surface liquid layer that is essential to lung homeostasis and defense. The understanding of how liquid is secreted in the lung is derived largely from studies of the airway epithelium. Comparatively little is known about liquid secretion mechanisms in the alveolar epithelium, including its cellular source. To define which cell type drives alveolar liquid secretion, we generated transgenic mice that expressed a Cftr-null allele in alveolar type 1 (AT1) cells, type 2 (AT2) cells, or both, then viewed liquid secretion in live alveoli using confocal microscopy of isolated, perfused lungs. Our findings show that liquid secretion was blocked in alveoli of all 3 transgenic mice, indicating that both AT1 and AT2 cells contribute to alveolar liquid secretion. Cftr-null expression in AT1 cells also blocked the secretion-mediated clearance of small particle and bacterial clusters from alveolar walls, indicating that AT1 cell CFTR contributes to alveolar defense. Together, these findings show alveolar liquid secretion depends on both AT1 and AT2 cell CFTR, and that CFTR in AT1 cells — a cell type not traditionally considered in liquid secretion mechanisms or CFTR-related lung diseases — contributes to lung liquid dynamics and host defense.

Authors

Sayahi Suthakaran, Sonya Homami, Deebly Chavez, Stephanie Tang, Sarah K.L. Moore, Chaya Sussman, Jimmy Zhang, Clemente J. Britto, Alice Prince, Alison J. May, Jaymin J. Kathiriya, Jaime L. Hook

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Figure 4

Dose-dependent relationship between AT1 cell Cftr deficiency and inhibition of AWL secretion in lungs of AT1-CFTRnull-GFP mice.

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Dose-dependent relationship between AT1 cell Cftr deficiency and inhibit...
(A–C) Confocal images (A) and group data (B and C) show AF-dextran fluorescence (yellow; 10 kDa, 10 mg/mL) after microinstillation in alveolar airspaces of lungs of AT1-CFTRnull-GFP mice. Experiments were carried out as indicated in Figure 3A. GFP fluorescence is not shown but was categorized in imaging fields of at least 30 alveoli as Low, Medium, and High as indicated in Figure 2. Images shown in the bottom row in A are reproduced from Figure 3C. In B and C, circles indicate n and each represent 1 trial of AF-dextran microinstillation in which mean fluorescence change was quantified in an imaging field of at least 30 alveoli. Trials were carried out in lungs of 3 mice but are presented according to the GFP fluorescence category (B) or the proportion of alveoli with GFP+ cells as a percentage of the total number of alveoli (C) in the imaging field. In C, the dashed line sets apart the 12 imaging fields in the High GFP fluorescence category, and the solid line was calculated by linear regression. Data are shown as mean ± SEM; *P < 0.05 by ANOVA with post hoc Tukey testing. Scale bars: 50 μm.