HTII-280, a Biomarker Specific to the Apical Plasma Membrane of Human Lung Alveolar Type II Cells

Gonzalez, Robert; Allen, Lennell; Gonzales, Linda W.; Ballard, Philip L.; Dobbs, Leland G.

doi:10.1369/jhc.2010.956433

Cited by 99 publications

(85 citation statements)

References 44 publications

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“…We have begun to address the question of whether AEC2s from human lungs are also long-term self-renewing stem cells able to give rise to alveolospheres in 3D culture. AEC2s were isolated using FACS based on expression of the surface marker HTII-280 (18). Immunohistochemistry of normal human lungs confirmed that HTII-280 and SFTPC colocalize, with HTII-280 being expressed on the luminal surface and SFTPC in the cytoplasm ( Figure 7A).…”

Section: Sftpc + Cells On the Periphery And Cells With Aec1 Markers Imentioning

confidence: 88%

Type 2 alveolar cells are stem cells in adult lung

et al. 2013

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Section: Sftpc + Cells On the Periphery And Cells With Aec1 Markers Imentioning

confidence: 88%

Type 2 alveolar cells are stem cells in adult lung

et al. 2013

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“…After lysing of the red blood cells, AECs were purified through a discontinuous gradient and subsequent positive selection with EpCAM microbeads (Miltenyi Biotec Inc., San Diego, CA). The purity of isolated type II cells was around 90%, as evaluated by staining the cells with pro-SP-C and ATII-280, an ATII-specific marker (14), by flow cytometry (data not shown). The purity was further increased during the primary cell culture.…”

Section: Methodsmentioning

confidence: 99%

Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

Travanty

Zhou

et al. 2015

J Virol

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Human alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection. IMPORTANCEDisease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection.

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“…Type II cells were isolated from donor lungs at 93% purity, as described (2). In some experiments, epithelial cells of adult peripheral lung were isolated by elastase treatment and FACS sorted, as previously described (17). Cells were initially treated with human IgG (50 g/ml; Sigma) to block nonspecific binding of mouse monoclonal primary antibodies against the type II cell-specific HTII-280 protein.…”

Section: Methodsmentioning

confidence: 99%

“…Cytospins of freshly isolated adult type II cells were fixed in 4% paraformaldehyde over night, washed, and stored at Ϫ20°C until use. Cytospins were permeabilized and stained for CEACAM6 (1:100) and HTII 280, a type II cell-specific marker in human lung (1:200) (17). Adult trachea sections were treated in a similar fashion and stained with CEACAM6 and rabbit anti-pan-cytokeratin (1:100, Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

Chapin

Bailey

Gonzales

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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PL. Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung. Am J Physiol Lung Cell Mol Physiol 302: L216 -L225, 2012. First published October 28, 2011 doi:10.1152/ajplung.00055.2011.-Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ϳ80% was the fully glycosylated, 90-kDa form that contains the glycophosphatidylinositol anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins (SP)-A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged, whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of adult lung, suggesting proximal-to-distal developmental expression in lung epithelium. In adult lung, most type I cells and ϳ50% of type II cells were immunopositive. We conclude that CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense. alveolar type II cells; lung lining fluid; surfactant; airway epithelium CARCINOEMBRYONIC CELL ADHESION molecule 6 (CEACAM6) (also called NCA, NCA-50/90, and CD66c) is a member of the carcinoembryonic antigen (CEA) gene family, consisting of 29 related genes. CEA proteins function as intercellular homophilic and heterophilic adhesion molecules and have signaling properties (18). CEACAM6 contains a glycophosphatidylinositol (GPI) membrane anchor (23) and is targeted to lipid rafts in apical membranes of polarized epithelial cells (26). CEACAM6 binds a variety of gram-negative bacteria and mediates internalization and phagocytosis, participating in innate immune defense in the intestine (13). The CEACAM6 gene is not present in rodents, and its emergence in primates may represent pathogen-host coevolution, providing different protein structures with selective bacterial binding properties.Expression of CEACAM6 and closely related CEACAM5 is deregulated and overexpressed in cancers of colorectal epithelium, with surface levels inversely correlated with both the degree of colonocyte differentiat...

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HTII-280, a Biomarker Specific to the Apical Plasma Membrane of Human Lung Alveolar Type II Cells

Cited by 99 publications

References 44 publications

Type 2 alveolar cells are stem cells in adult lung

Type 2 alveolar cells are stem cells in adult lung

Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

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