CD208/Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

Abstract

Dendritic cell-lysosomal associated membrane protein (DC-LAMP)/CD208, a member of the lysosomal associated membrane protein (LAMP) family, is specifically expressed by human DCs on activation. However, its mouse counterpart could not be detected in mature DCs. The present study demonstrates that DC-LAMP is constitutively expressed by mouse, sheep, and human type II pneumocytes. Confocal and immunoelectron microscopy showed that mouse DC-LAMP protein co-localizes with lbm180, a specific marker for the limiting membrane of lamellar bodies that contain surfactant protein B, as well as with intracellular MHC class II molecules that accumulate in the same organelles. Expression of DC-LAMP was also occasionally detected at the cell surface of type II pneumocytes. Interestingly, human bronchioloalveolar carcinoma tumor cells, which correspond to transformed type II pneumocytes, express DC-LAMP. Similar observations were made in the Jaagsiekte sheep retrovirus-associated ovine pulmonary adenocarcinoma, a model of human bronchioloalveolar carcinoma. This study establishes that DC-LAMP is constitutively expressed in normal type II pneumocytes. Furthermore, DC-LAMP appears to be a marker of transformed type II pneumocytes as well, an observation that may help the study and the classifica- The lysosomal associated membrane protein (LAMP) family consists of a group of heavily glycosylated proteins accounting for approximately half of the protein content in the lysosomal membrane. They all contain a conserved intracytoplasmic tyrosine-based lysosome-targeting motif YXX (where represents a bulky hydrophobic residue).1 Several members of this family (LAMP-1 to LAMP-3 and CD68) were cloned in a broad range of species.1 Although LAMP-1 and LAMP-2 are ubiquitously expressed, 2 CD68 is mainly restricted to monocytes and macrophages.3 The latest human LAMP protein identified, DC-LAMP/CD208, was originally described as a molecule specifically expressed in mature dendritic cells (DCs). 4 DC-LAMP appears transiently on DC activation at the limiting membrane of the MHC class II-containing intracellular compartments (MIIC) 4,5 involved in MHC class II peptide loading and transport to the cell surface. 5On further maturation, MHC class II molecules and DC-LAMP segregate: MHC class II molecules are translocated to the cell surface membrane, whereas DC-LAMP concentrates in perinuclear lysosomes. On the basis of these observations, it was proposed that DC-LAMP could play a role in the sorting of the MIIC membrane-associated molecules and the transfer of MHC class II molecules to the cell surface. 4 Human, monkey, and mouse DC-LAMP mRNAs were shown to be expressed in the lung 4,6 -8 but the cellular source was not determined. Of note, murine DC-LAMP was not detected in mouse DCs. 8 In the present study, using specific monoclonal antibodies, we establish that DC-LAMP is specifically expressed by mouse, sheep, and human type II pneumocytes (PnIIs). PnIIs are peripheral pulmonary cells acting as stem cells for repopulation of lung by alve...

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

“…Cell specificity of CD208 (also known as dendritic cell-lysosomal associated membrane protein) expression in human, murine and ovine lungs is histologically, morphologically, biochemically and ultrastructurally consistent with type II pneumocytes [18]. The type II pneumocyte is an important cell in this region as it functions not only as a stem cell for alveolar type I pneumocytes, but also as regulator of surfactant and innate immune molecule expression in the terminal airway.…”

“…type II pneumocytes) assessed by LCM. In humans, mice and sheep, type II pneumocytes are characterized by CD208+ expression [18]. SP-A expression has been classically linked to type II pneumocytes, however, less robust expression occurs in other cells of the lung and extrapulmonary expression has also been described [28].…”

“…The type II pneumocyte is an important cell in this region as it functions not only as a stem cell for alveolar type I pneumocytes, but also as regulator of surfactant and innate immune molecule expression in the terminal airway. Cellular expression products of the terminal airway that have putative (direct or indirect) anti-viral activity include surfactant proteins A and D (SP-A and SP-D, respectively) [19], toll-like receptor 4 (TLR4, [20]) and beta defensins [18]. A role for these immune factors in paramyxoviral clearance was recently characterized by increased expression levels of ovine surfactant proteins A and D (SP-A, SP-D) and sheep beta defensin 1 (SBD1) in PIV3-infected newborn lambs and the timing of this increased expression was associated with viral clearance [10].…”

Lung epithelial branching program antagonizes alveolar differentiation

“…S7), the Sox9 mutant lung also up-regulated a number of genes, including Sftpb, Sftpc, Lamp3, Napsa, and Ctsh, that are known or were shown (Fig. S12A) to be expressed by differentiated alveolar cells and involved in the production and processing of surfactant proteins (41,42).…”

Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep

“…Interestingly, tumoural cells overexpress CD208/DC-LAMP (Dendritic Cell Lyzosomal Associated Membrane Protein) [74], a protein belonging to the LAMP family of proteins (LysosomalAssociated Membrane Protein), and initially described in activated dendritic cells. CD208/DC-LAMP is also constitutively expressed in human, murine and ovine type II pneumocytes, and is over-expressed in human bronchioloalveolar carcinoma and OPA [74].…”