Alveolar epithelial type II cell: defender of the alveolus revisited

Abstract

In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

Figure 1

Human lung AE2 cells. (a) Scanning electron micrograph of human lung. Two AE2 cells (P2) are seen to protrude above the largely smooth alveolar epithelial surface. A pore of Kohn (K) and the cell–cell junction (arrowheads) between two AE1 cells are denoted. (b) Transmission electron micrograph of human AE2 cell displaying typical ultrastructural features, such as lamellar bodies (Lb) and apical microvilli (arrows). Nu = nucleus.

Figure 2

Indirect immunofluorescence double labelling of rat parenchyma. (a) AE2 cells are stained for surfactant protein D (green) and contrasted by labelling of AE1 cells with Lycopersicon esculentum lectin (red). (b) AE2 cell double-labelled for surfactant protein C (red) and adhesion molecule CD44v6 (green).

Figure 3

Transmission electron micrograph of canine lamellar body at high power magnification. The densely packed stacks of phospholipid membranes are bound by a single limiting membrane (arrowheads).

Figure 4

Transmission electron micrograph of rat intra-alveolar surfactant with the typical lattice-like appearance of tubular myelin, which is in close contact with the alveolar lining layer (arrowheads). Vesicular surfactant (small arrows) is seen near the apical surface of the alveolar epithelium.

Figure 5

Indirect immunoperoxidase staining of rat lung for proliferation marker Ki-67. One day after instillation of recombinant human KGF, many epithelial cells at alveolar corners, the typical AE2 cell location, exhibit nuclear staining. The cell in the centre is just about to complete mitosis.

Figure 6

Transmission electron micrograph of apoptotic AE2 cells (*) engulfed by their AE2 cell neighbours at day 5 after intrabronchial instillation of recombinant human KGF into rat lung in vivo. A = air space; Lb = lamellar bodies; Nu = nuclei of phagocytic AE2 cells.