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...