The alveoli are lined with two types of cell, the Type I and Type II pneumocytes.

The Type I pneumocyte is a very large, thin cell stretched over a very large area. This cell cannot replicate and is susceptible to a large number of toxic insults. Type I pneumocytes are responsible for gas exchange occurring in the alveoli.

The Type II granular pneumocyte is a roughly cuboidal cell that is usually found at the alveolar septal junctions. Type II cells cover about 5% of the surface area of the alveoli, whereas type I pneumocytes (because of their squamous shape) cover 95% of the total area. Even though they cover less surface area, type II cells greatly outnumber type I cells. Type II cells are responsible for the production and secretion of surfactant. The Type II pneumocyte can replicate in the alveoli and will replicate to replace damaged Type I pneumocytes.

Alkaline Phosphatase

• Heat-stable alkaline phosphatase is a marker for human and monkey type-I pneumocytes. PMID: 2357723
• a typical marker of type II pneumocyte maturation. PMID: 8761368

Aquaporin 5 (Aqp-5)

• a type-I pneumocyte marker. PMID: 15917467, PMID: 11748153
• present on the apical membrane of epithelial cells in various secretory glands as well as on the apical membrane of the airway epithelium, airway submucosal glands, and type 1 pneumocytes, where it can participate in respiratory tract water homeostasis. PMID: 15536076
• localized to the apical plasma membrane of type I pneumocytes and the apical plasma membranes of secretory epithelium in upper airway and salivary glands. PMID: 9374640

Bauhinia purpurea lectin (BPL)

• a type I pneumocyte-specific marker. PMID: 7894248, PMID: 8088898

Caveolins (Cav-1, -2, and -3)

• a gene family of cytoplasmic membrane-anchored scaffolding proteins that: (i) help to sculpt caveolae membranes from the plasma membrane proper; and (ii) participate in the sequestration of inactive signaling molecules. PMID: 9662443
• caveolin-1 (also called caveolin, Cav-1 and VIP2I) are found in terminally-differentiated cell types, such as adipocytes, endothelia, smooth muscle cells, and type I pneumocytes. PMID: 15003112
• Caveolin-2 (Cav-2) is colocalized and coexpressed with Cav-1 and requires Cav-1 for proper membrane targeting. PMID: 15003112
• In the adult, caveolin-1 and -2 are co-expressed and are most abundant in type I pneumocytes, endothelia, fibroblastic cells and adipocytes, while the expression of caveolin-3 is restricted to striated muscle cells. PMID: 9662443

CD44v6

• marker for type II pneumocytes. PMID: 15974816
• Strong positivity for CD44v6 was observed in the basal cells of bronchial epithelium, squamous metaplasia, and type II pneumocytes. PMID: 12940087, PMID: 9224749
• Nonneoplastic adult lung showed CD44v6 expression that was restricted to epithelial cells with membranous staining of basal bronchial cells and squamous metaplasia as well as basolateral membranous staining of type 2 pneumocytes. PMID: 9210706
• CD44v isoforms containing exon v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells with a strong basolateral distribution pattern in the entire population of type II pneumocytes and in basal cells of the bronchial epithelium, and it may be utilized by type II pneumocytes in epithelial-mesenchymal interactions and in the maintenance of the pulmonary histoarchitecture. PMID: 7576702

CD208 (DC-LAMP)

• may serve as a marker for pneumocyte maturation in the developing fetal lung. PMID: 16899762, PMID: 16510184
• a member of the lysosomal associated membrane protein (LAMP) family, is a marker of normal and transformed type II pneumocytes. PMID: 14982840

CP4

• a pneumocyte-derived collagenous surfactant-associated protein. PMID: 3219363

Cx43

• detected in pneumocytes type II and I, in large blood vessel endothelia, in peribronchial smooth muscle cells, and in some peribronchial and perivascular interstitial cells. In severely injured lungs (about 3 months after irradiation), Cx43 was found also in the cytoplasm of type II pneumocytes. PMID: 8911970

DC-LAMP (CD208)

• constitutively expressed by mouse, sheep, and human type II pneumocytes, is a marker of normal and transformed type II pneumocytes. PMID: 14982840

gp600

• the reactive epitopes for anti-gp600 in lung parenchyma are exclusively localized on type II pneumocytes and have a Mr of approximately 270 to 290 kDa and that anti-gp600 may be used as a specific immunologic marker for the type II pneumocytes. PMID: 2647848

HTI56

• a marker of terminally differentiated type I pneumocytes. PMID: 10706135

ICAM-1

• ICAM-1 detectable in the normal lung, was also detected on the pneumocyte cell surface at all stages of acute rejection, suggesting that pneumocytes were target cells for LFA-1 positive cells. PMID: 7959589
• Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells. PMID: 10594564

KL-6

• a mucin-like glycoprotein expressed on type II pneumocytes. PMID: 14738246
• one of the MUC1 antigens, is a mucin-like high-molecular-weight glycoprotein, which is strongly expressed on type II pneumocytes. PMID: 12924525
• a mucin-like high molecular weight glycoprotein secreted by proliferating type II alveolar pneumocytes, has been identified as a potential marker of interstitial pneumonitis. PMID: 11927785
• a mucin-like high-molecular-weight glycoprotein, is expressed on type-2 pneumocytes and bronchiolar epithelial cells. PMID: 11557124, PMID: 10733471
• a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. PMID: 10782818,
• a MUC1 mucin preferentially expressed in regenerating type 2 pneumocytes. PMID: 9415357

MUC1

• marker for type II pneumocytes. PMID: 15974816
• a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis. PMID: 9850098
• marker of the type II pneumocyte progenitor cell lineage. PMID: 11948134, PMID: 10706135

RAGE (receptor for advanced glycation end products)

• In normal lung low expression of the receptor was observed in bronchiolar epithelia, type II pneumocytes, macrophages and some endothelia. In all pathological conditions associated with inflammation and lung damage overexpression of both the receptor and of AGEs was observed in bronchiolar epithelia, type II alveolar pneumocytes, alveolar macrophages and endothelia. PMID: 16941014
• a cell surface multiligand receptor of the immunoglobulin superfamily, expressed in the cytoplasm of pneumocytes. PMID: 15933755
• Anti-RAGE immunoreactivity was prominent in alveolar epithelial type I pneumocytes, while it was absent from type II pneumocytes and capillary endothelium. PMID: 9846897

Surfactant Protein A,  B, C, and D

• surfactant protein A (SP-A) is a distinct marker for type II pneumocytes. PMID: 12924525
• SP-A production is a marker of type II pneumocyte differentiation. PMID: 10745024
• SP-A is a major pulmonary surfactant protein produced by type II pneumocytes. PMID: 8425584
• Surfactant protein (SP)-B expression is restricted to type II pneumocytes and Clara cells in the lung. PMID: 11152647
• surfactant protein C is a type II pneumocyte-specific gene. PMID: 15268776, PMID: 9498406
• surfactant protein-D (SP-D) is produced by type II pneumocytes. PMID: 11061091

T1alpha

• a type I pneumocyte marker. PMID: 11748153

Thomsen-Friedenreich antigen

• marker for type II pneumocytes. PMID: 15974816, PMID: 10603446

TF antigen

• directly expressed on the apical surface of some type II pneumocytes in the pulmonary sarcoidosis specimens. PMID: 10453879
• express abundantly in type II pneumocytes. PMID: 10071237
• In patients with IPF, IP-SSc, and idiopathic BOOP, the TF antigen was positively stained in type II pneumocytes and in some alveolar macrophages. Neither TF antigens nor TF-mRNA were detected in the normal lung. These results indicate that type II pneumocytes are a major source of TF, suggesting that TF production in these cells is closely related to fibrin deposition in the lungs of people with these diseases. PMID: 9279250

Thyroid Transcription Factor 1 (TTF-1)

• marker for type II pneumocytes. PMID: 15974816
• a 38-kd homeodomain containing DNA-binding protein originally identified in follicular cells of the thyroid and subsequently in pneumocytes. PMID: 12051643
• a 38-kd protein, located primarily in the nucleus of type 2 pneumocytes and clara cells. PMID: 11679943, PMID: 11075855