Type Ii Pneumocyte Lamellar Bodies Contain Components Of The Niemann-Pick Type C (Npc) Pathway

Type II cell lamellar bodies, the primary storage organelle for lung surfactant, contain about 10% cholesterol. Cellular cholesterol trafficking has been shown to be regulated by the NPC pathway. A form of alveolar proteinosis characterized by high cholesterol to phospholipid ratio has been reported in an NPC2 patient, which suggested the NPC pathway played a role in regulating surfactant cholesterol in type II cells. Our objective was to define the localization and function of components of the NPC pathway in alveolar type II cells. Immunocytochemical analysis for NPC1, NPC2, and lysosomal acid lipase (LAL) was performed in isolated primary rat type II cells. The ATP‐binding cassette transporter (ABCA3) was used to identify the limiting membrane of lamellar bodies. 3D projections of a single lamellar body acquired by confocal microscopy confirmed NPC1 expression along the entirety of the limiting membrane. NPC1 was localized in alternating adjacent domains with ABCA3. NPC2 and LAL were located within the lumen of the organelle. Upon pharmacological inhibition of the NPC pathway with U18666A compound, cholesterol was found to accumulate within lamellar bodies. These results suggest that the NPC pathway is important for regulating lamellar body cholesterol. [HL‐19737 and NRSA T32‐HL‐07748‐17]