Human dendritic cell lysosome-associated membrane protein expressed in lung type II pneumocytes

Akasaki, Kenji; Nakamura, Nobuki; Tsukui, Naoko; Yokota, Sadaki; Murata, Shin Ichi; Katoh, Ryohei; Michihara, Akihiro; Tsuji, Hiroshi; Marques, Ernesto T. A.; August, J. Thomas

doi:10.1016/j.abb.2004.02.042

Cited by 17 publications

(21 citation statements)

References 39 publications

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“…In hormone-induced, differentiated human fetal lung ATII cells, which produce and secrete surfactant comparable with adult ATII cells (15), confocal microscopy showed hABCA3-GFP in the membranes of vesicles that were labeled with the lysosomal marker LysoTracker Red and the lamellar body membrane marker dendritic cellspecific lysosome-associated membrane protein (DC-LAMP) ( Fig. 1, a-f)) (25). In A549 cells, a lung-derived epithelial tumor cell line that neither contains lamellar bodies nor expresses DC-LAMP and surfactant proteins (26), hABCA3-GFP, was found in membranes of vesicles that were labeled with LysoTracker Red and two lysosomal membrane proteins, LAMP-1 and LAMP-2 ( Fig.…”

Section: Habca3 Localizes To Lamellar Bodies and Lysosomes-abca3mentioning

confidence: 99%

Functional and Trafficking Defects in ATP Binding Cassette A3 Mutants Associated with Respiratory Distress Syndrome

Cheong

Madesh

Gonzales

et al. 2006

Journal of Biological Chemistry

180

164

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Silencing of ABCA3 expression also reduced vesicular uptake of surfactant lipids phosphatidylcholine, sphingomyelin, and cholesterol but not phosphatidylethanolamine. We conclude that ABCA3 is required for lysosomal loading of phosphatidylcholine and conversion of lysosomes to lamellar body-like structures. ATP binding cassette (ABC)2 transporters are a superfamily of highly conserved membrane proteins that transport a wide variety of substrates across cell membranes (1). Among the several subfamilies, the ABCA subclass has received considerable attention, because mutations of the ABCA1 gene cause Tangier disease and mutations of the ABCA4 gene cause Stargardt macular dystrophy in humans (2-5). ABCA1 and ABCA4 are proposed to be transmembrane transporters for intracellular cholesterol/phospholipids and N-retinylidene phosphatidylethanolamine, respectively (3-5). ABCA3, a member of the ABCA subfamily with unknown function (6 -10), is predominantly expressed in the lung and localized to the limiting membrane of lamellar bodies in alveolar epithelial type II cells (ATII) in both humans and rats (7,8).In the lung, development of structures for effective pulmonary gas exchange and production of pulmonary surfactant are necessary for successful adaptation to extrauterine life in the newborn infant. These key processes in lung maturation require differentiation of epithelium into ATII cells, the cellular source for surfactant. Pulmonary surfactant is a complex mixture of lipids, primarily phosphatidylcholine (60 -70% of which is dipalmitoylphosphatidylcholine) and specific proteins that line the alveolar surface of the lung, reducing surface tension at the air-liquid interface and preventing collapse of the lung on expiration (11). Surfactant is assembled and stored in lamellar bodies, the secretory organelles of ATII cells (11-13). Two other members of the ABCA subfamily, ABCA1 and ABCA4, have been implicated in lipid transport leading to the hypothesis that ABCA3 transports lipid into the lamellar bodies of ATII cells (7-9). Recently, it has been reported that mutations in ABCA3 are associated with defective assembly of lamellar bodies and fatal respiratory distress syndrome (RDS) in the newborn infant and interstitial lung disease (6, 10).To study the potential role of ABCA3 in RDS, we examined the subcellular trafficking and substrate specificity of ABCA3 in hATII cells and mammalian cell lines using green fluorescent protein (GFP)-tagged protein and fluorescent lipid analogs. Morphological and functional changes secondary to both loss-and gain-of-function experiments demonstrate that ABCA3 selectively transports phosphatidylcholine, sphingomyelin, and cholesterol to lamellar bodies in hATII cells. Our findings indicate that lipid trafficking by ABCA3 across lamellar body membranes is necessary for lamellar body biogenesis as a key step in assembly of lung surfactant in hATII cells.

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Section: Habca3 Localizes To Lamellar Bodies and Lysosomes-abca3mentioning

confidence: 99%

Functional and Trafficking Defects in ATP Binding Cassette A3 Mutants Associated with Respiratory Distress Syndrome

Cheong

Madesh

Gonzales

et al. 2006

Journal of Biological Chemistry

180

164

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“…LAMP-1 is expressed constitutively at high levels by all cells, including immature dendritic cells (DC), and is one of the most glycosylated proteins known to date. A recently identified member of the LAMP family, designated DC-LAMP, is specifically expressed in the endosomal/lysosomal compartments of human mature DC (37) and lung type II pneumocytes (38,39). This human DC-LAMP differs biochemically from the other LAMP molecules primarily in bearing a mucin-like sugar structure containing several putative O-linked glycans that are localized to the amino-terminal half of its luminal domain.…”

Section: T He Establishment Of Mhc-restricted Cd4mentioning

confidence: 99%

“…The DC-LAMP plasmid was constructed from cDNA obtained from a human lung tissue library (GenBank accession no. AB013924) (38). The DC-LAMP luminal domain was amplified by PCR using primers bearing an NheI site at the 5Ј end and an XhoI site at the 3Ј end; the transmembrane domain was inserted with EcoRI and KpnI sites at the 5Ј and 3Ј ends, respectively.…”

Section: Plasmidsmentioning

confidence: 99%

“…The LAMP/gag construct has been described previously (24). The DC-LAMP plasmid was constructed from cDNA obtained from a human lung tissue library (38). The DC-LAMP/gag chimera was made similarly by replacing the LAMP-1 luminal and transmembrane domain sequences with the respective DC-LAMP homologous sequences.…”

Section: Lamp/gag and Dc-lamp/gag Chimeras Traffic Differentially Thrmentioning

confidence: 99%

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Dendritic Cell-Lysosomal-Associated Membrane Protein (LAMP) and LAMP-1-HIV-1 Gag Chimeras Have Distinct Cellular Trafficking Pathways and Prime T and B Cell Responses to a Diverse Repertoire of Epitopes

Arruda

Sim²,

Chikhlikar

et al. 2006

The Journal of Immunology

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Ag processing is a critical step in defining the repertoire of epitope-specific immune responses. In the present study, HIV-1 p55Gag Ag was synthesized as a DNA plasmid with either lysosomal-associated membrane protein-1 (LAMP/gag) or human dendritic cell-LAMP (DC-LAMP/gag) and used to immunize mice. Analysis of the cellular trafficking of these two chimeras demonstrated that both molecules colocalized with MHC class II molecules but differed in their overall trafficking to endosomal/lysosomal compartments. Following DNA immunization, both chimeras elicited potent Gag-specific T and B cell immune responses in mice but differ markedly in their IL-4 and IgG1/IgG2a responses. The DC-LAMP chimera induced a stronger Th type 1 response. ELISPOT analysis of T cell responses to 122 individual peptides encompassing the entire p55gag sequence (15-aa peptides overlapping by 11 residues) showed that DNA immunization with native gag, LAMP/gag, or DC-LAMP/gag induced responses to identical immunodominant CD4+ and CD8+ peptides. However, LAMP/gag and DC-LAMP/gag plasmids also elicited significant responses to 23 additional cryptic epitopes that were not recognized after immunization with native gag DNA. The three plasmids induced T cell responses to a total of 39 distinct peptide sequences, 13 of which were induced by all three DNA constructs. Individually, DC-LAMP/gag elicited the most diverse response, with a specific T cell response against 35 peptides. In addition, immunization with LAMP/gag and DC-LAMP/gag chimeras also promoted Ab secretion to an increased number of epitopes. These data indicate that LAMP-1 and DC-LAMP Ag chimeras follow different trafficking pathways, induce distinct modulatory immune responses, and are able to present cryptic epitopes.

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“…DC-LAMP, the human lysosome-associated membrane, protein-3, was originally described as a molecule specifically expressed by mature dendritic cells (12,13). Its expression is induced in the later stages of maturation.…”

mentioning

confidence: 99%

Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

Elliott

Scolyer

Suciu

et al. 2007

Clinical Cancer Research

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Purpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP + DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs. Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP + DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and z200/mm 2 ). Results: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP + DC scores (j score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).Conclusion: This study is the first to report the prognostic value of DC-LAMP + DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (z200/mm 2 ) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.

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Human dendritic cell lysosome-associated membrane protein expressed in lung type II pneumocytes

Cited by 17 publications

References 39 publications

Functional and Trafficking Defects in ATP Binding Cassette A3 Mutants Associated with Respiratory Distress Syndrome

Functional and Trafficking Defects in ATP Binding Cassette A3 Mutants Associated with Respiratory Distress Syndrome

Dendritic Cell-Lysosomal-Associated Membrane Protein (LAMP) and LAMP-1-HIV-1 Gag Chimeras Have Distinct Cellular Trafficking Pathways and Prime T and B Cell Responses to a Diverse Repertoire of Epitopes

Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

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