Alveolar type 2 (AT2) cells are specialized cells located deep within the lungs. These cells play a role in maintaining the basic operations of the lungs, performing functions fundamental for breathing and lung health.
The Architecture of the Alveoli
The lungs contain millions of tiny air sacs known as alveoli, which are the primary sites where gas exchange occurs. Each alveolus is a hollow, distensible, cup-shaped cavity that facilitates the transfer of oxygen into the bloodstream and carbon dioxide out of it. Alveoli are surrounded by a network of capillaries, forming a thin blood-air barrier for efficient gas exchange.
The alveolar walls primarily consist of two types of epithelial cells: alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. AT1 cells are thin, flat, and squamous, covering about 95% of the alveolar surface area. Their flattened shape and attenuated nature create an optimal surface for the rapid diffusion of gases.
In contrast, AT2 cells are cuboidal in shape and are interspersed among the AT1 cells, clustering in the corners of the alveoli. While AT2 cells only cover about 5% to 7% of the alveolar surface, they are more numerous than AT1 cells, with a cell ratio of roughly 1:1 or 6:4 between AT1 and AT2 cells.
Producing Pulmonary Surfactant
A primary function of AT2 cells is the production and secretion of pulmonary surfactant. This complex mixture, primarily composed of lipids and proteins, is stored within characteristic lamellar bodies inside the AT2 cells before being released into the alveolar lining fluid. The main lipid component, dipalmitoylphosphatidylcholine (DPPC), along with other phospholipids, makes up about 80% of the surfactant.
Pulmonary surfactant also includes specific surfactant proteins (SP-A, SP-B, SP-C, and SP-D), which contribute to the surfactant’s stability and function. SP-B and SP-C are hydrophobic and work with DPPC to reduce surface tension. SP-A and SP-D are hydrophilic and play a role in the lung’s immune defense by binding to pathogens.
The purpose of this surfactant is to reduce the surface tension at the air-liquid interface within the alveoli. This reduction prevents the tiny air sacs from collapsing entirely during exhalation, making it much easier for the lungs to inflate with each breath. Without this oily coating, the cohesive forces of water molecules lining the alveoli would cause them to collapse.
Serving as Progenitor Cells
Beyond surfactant production, AT2 cells also function as local progenitor, or stem, cells for the alveolar epithelium. This means they have the capacity to divide and differentiate into new cells when the lung tissue is damaged. When the delicate AT1 cells, which are susceptible to various injuries, are compromised, AT2 cells are activated.
Upon damage, AT2 cells proliferate and then undergo a transformation process. They differentiate into new AT1 cells, effectively repairing the thin lining of the alveoli that is responsible for gas exchange. This regenerative capability highlights their role in maintaining the structural integrity and functional capacity of the lung’s gas exchange surface.
Role in Lung Injury and Disease
The proper functioning of AT2 cells is connected to several lung diseases, where their dysfunction or death can lead to health consequences. When AT2 cells are compromised, the lung’s ability to produce surfactant and repair itself is impaired, setting the stage for disease progression.
In Acute Respiratory Distress Syndrome (ARDS), severe lung injury leads to the widespread loss of AT2 cells. This loss results in a significant deficiency of pulmonary surfactant, causing the alveoli to collapse and fluid to leak into the air sacs. The impaired gas exchange in ARDS leads to severe breathing difficulties and reduced oxygen levels in the blood.
Pulmonary fibrosis, particularly Idiopathic Pulmonary Fibrosis (IPF), is another condition where AT2 cell dysfunction plays a central role. Instead of properly regenerating the alveolar lining, abnormal AT2 cell repair processes contribute to the formation of scar tissue. This leads to a progressive stiffening of the lungs and a decline in lung function.