Type II Pneumocytes

The alveolar type II cells are spherical pneumocytes which comprise only 4% of the alveolar surface area, yet they constitute 60 % of alveolar epithelial cells and 10-15 % of all lung cells. Four major functions have been attributed to alveolar type II cells  

4) Regeneration of the alveolar epithelium following lung injury. 

Therefore, alveolar type n cells play important roles in normal pulmonary function and in the response of the lung to toxic compounds, which may cause lung damage. 

Several methods have been employed to isolate and purify type II cells, including enzymatic digestion of pulmonary tissue to free lung cells from the pulmonary epithehum and purification of type II pneumocytes by discontinuous density gradients (Kikkawa and Yoneda 1974), primary culture (Dobbs and Mason 1979), centrifugal elutriation (Jones et al. 1982), or unit gravity sedimentation (Brown et al. 1984). 

Type II pneumocytes can be identified at the hght microscope level by antibodies against cyto-keratin 18 (Schlichenmaier et al. 2000). This intermediate filament was thereby predominantly lo-cahsed in the apical compartment and the intensity of the immunostaining depends on the stage of development. Type I alveolar cells as well as alveolar 

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Complement (C3a, C5a) Macrophages, type II pneumocytes and fibroblasts Microbes Opsinization by phagocytes and chemotaxis Increased activity after exposure to LPS and allergens ozone, diesel, cigarette [23, 28]... 

It is commonly known that lipids, carbohydrates, and glycolipids are present in the Golgi apparatus (27). The determination of the components that react with the ZIO mixture was carried out by removing each component from tissues before incubation in the ZIO mixture. After lipid extraction by acetone (14), chloroform-methanol (15), or propylene oxide (27), no osmium-zinc precipitates could be detected in structures that normally reacted with ZIO. Blumcke et al. (15) summarized the nature of the lipids that react with the ZIO mixture as follows lipids and lipoproteins of cell membranes, neutral fat droplets (41), and lipid globules of type II pneumocytes and alveolar macrophages were, however, not as electron dense as the normally reactive lamellae containing highly unsaturated fatty acids. 

Blumcke WD, Kessler HR, Niedorf NH, Veith FJ. Ultrastructure of lamellar bodies of type II Pneumocytes after osmium-zinc impregnation. J Ultrastruct Res 1973 42 417-433. 

Fehrenbach H, Schmiedl A, Wahlers T, Hirt SW, Brasch F, Riemann D, Richter J (1995) Morphometric characterisation of the fine structure of human type II pneumocytes. Anat Rec 243(1 ) 49-62... 

Bingle L, Bull TB, Fox B, Guz A, Richards RJ, Tetley TD (1990) Type II pneumocytes in mixed cell culture of human lung a light and electron microscopic study. Environ Health Perspect 85 71-80... 

At the distal respiratory site, the alveolar epithelial cell layer is much flatter (0.1 -0.5 pm) and composed of two major cell types, squamous type I and agranular type II pneumocytes. Type I pneumocytes are non-phagocytic and highly flattened cells with broad and thin extensions. They occupy -95 % of the alveolar luminal surface, although they are less numerous than type II cells. The remaining surface is occupied by type II pneumocytes, which have blunt microvilli and contain multivesicular bodies [3, 11]. 

Type I pneumocytes, joined with endothelial cells by fused basement membranes, offer a very short airways-blood pathway for the diffusion of gases and drug molecules. They are known to contain numerous endocytotic vesicles which play an important role in the absorption process of proteins and transcellular movement of transporters [12, 13]. The functions of type II pneumocytes are well studied and include... 

Hydrophilic surfactant proteins A (SP-A) and D (SP-D), secreted by type II pneumocytes, interact specifically with a wide range of microorganisms and play important roles in the innate, natural defense system of the lung [16]. Both mRNA and protein levels of SP-A and SP-D increase dramatically in response to lung infection, injury and endotoxin challenge [17]. Type II pneumocytes also express class II major histocompatibility complex (MHC) antigens and intracellular adhesion molecule (ICAM-1), which may facilitate pulmonary immune responses [15]. 

Helliwell, P.A., D. Meredith, C.A. Boyd, J.R. Bronk, N. Lister, and P.D. Bailey. 1994. Tripeptide transport in rat lung. Biochim. Biophys. Acta 1190 430-434. Meredith, D., and C.A. Boyd. 1995. Dipeptide transport characteristics of the apical membrane of rat lung type II pneumocytes. Am.]. Physiol. 269 L137-L143. 

Type-II pneumocytes cuboidal cells that store and secrete pulmonary surfactant. 

Type I pneumocytes make up most of the epithelial surface. It is the large, thin, type I pneumocytes that are the primary site of pulmonary protein absorption. The type II pneumocytes, lying in niches between type I cells, are the main source of surfactants and also replace type I cells as they undergo apoptosis (programmed cell death) after about 120 days. 

Three patients with busulfan-induced interstitial pneumonitis each had circulating immune complexes and alveolitis, and histology demonstrated consistent abnormalities of type I pneumocytes and depletion of type II pneumocytes (7). 

Adult rats were exposed to different concentrations of n-hexane and lung tissue was then examined. The direct toxic effect to pneumocytes could be demonstrated as definite regressive alterations, such as fatty generation and change of lamellar bodies of type II pneumocytes as well as increased detachment of cells. After chronic inhalation of solvents, conspicuous aggregation of lamellar discharge material of type II pneumocytes can be seen and, probably as a result of an irritated fat metabolism, there were large lysosome-like bodies with densely packed lipid material in type I pneumocytes. 

The type II pneumocytes synthesize phosphatidylcholine in a fashion quite different from that in other cells. Most other cells synthesize phosphatidylserine from cytidine diphosphate diacylglycerol and serine. The phosphatidylserine is then decarboxylated to yield phosphatidyl ethanoiamine. The final step is the successive donation of three methyl groups via S-adenosylmethionine to form phosphatidylcholine. The pulmonary biosynthetic pathway is shown in Figure 54-2. The enzyme choline phosphotransferase forms PC directly from cytidine diphosphocholine and diacylglycerol. Phosphatidylinositol formation peaks at about 35 weeks. As PI decreases in concentration, PG begins to increase. 

Nardone LL, Andrews SB (1979) Cell line A549 as a model of the type II pneumocyte. Phospholipid biosynthesis from native and organometallic precursors. Biochim Biophys Acta 573(2) 276-295... 

Haller T, Auktor K, Frick M et al (1999) Threshold calcium levels for lamellar body exocytosis in type II pneumocytes. Am J Physiol 277(5 Pt 1) L893-L900... 

Chen M, Brown LA (1990) Histamine stimulation of surfactant secretion from rat type II pneumocytes. Am J Physiol 258(4 Pt 1) L195-L200... 

Romero C, Benito E, Bosch MA (1995) Effect of Escherichia coli lipopolysaccharide on surfactant secretion in primary cultures of rat type II pneumocytes. Biochim Biophys Acta 1256(3) 305-309... 

Nishina K, Mikawa K, Morikawa O et al (2002) The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblasts. Anesth Analg 94(2) 385-388, table of contents... 

The EC-SOD is less responsive to oxidant stress than MnSOD. However, in human fibroblasts, the level of SOD3 is elevated by interferon (IFN)-y and IL-1 [94]. In rat alveolar type II pneumocytes, TNF-a and INF-y elevate SOD3 expression via activation of NF-kB [95]. In vascular smooth muscle cells, expression of EC-SOD is induced by INF-yand IL-4 [96]. Angiotensin II up-reg-ulates EC-SOD synthesis in vascular smooth muscle cells [30]. 

RDS is attributed primarily to insufficient formation and differentiation of type II pneumocytes with consequent impaired production and release of surfactant. Pulmonary surfactant contains phospholipids that function at the air-liquid interface in the alveolus to lower surface tension, thus preventing alveolar collapse. In the face... 

Natural human surfactant contains 85% phospholipids, 10% neutral lipids, and 5% surfactant proteins or apolipoproteins. Animal surfactants have similar protein and lipid content. Surfactant is synthesized in type II pneumocytes in the alveoli. After secretion, the major... 

Napsin-A (Nap-A) is an aspartic proteinase that is expressed in normal lung parenchymal type II pneumo-cytes, and in proximal and convoluted tubules of the kidney. It is present in lysosomes of type II pneumocytes... 

Tatrai, E. et al., Comparative in vitro toxicity of cadmium and lead on redox cycling in type II pneumocytes, J. Appl Toxicol, 21, 479, 2001. 

Thyroid transcription factor-1 (TTF-1) Lung cancer (adenocarcinoma, small cell carcinoma), thyroid tumors Small cell carcinoma of different locations Type II pneumocytes and Clara cells of lung, thyroid follicular and parafollicular C cells, diencephalon... 

In the lungs, HDL is the primary source of vitamin E for type II pneumocytes, and its uptake is regulated by the expression of scavenger receptor SR-BI. In the brain, HDL-associated a-tocopherol is selectively transferred into cells constituting the blood-brain barrier via SR-BI. Similarly, SR-BI transports HDL-associated a-tocopherol coming from the periphery back into the liver, where it is again specifically recognized by a-TTP, recycled, and secreted in VLDL. ... 

Chemokines also are produced by nonmyeloid cells in the lungs, including type II pneumocytes, fibroblasts, pleural mesothelial cells, and endothelial cells. In general, these parenchymal cells do not respond directly to LPS, but produce IL-8 and MCP-1 in response to the acute pro-inflammatory cytokines TNFa and IL-ip (49-54). Endothelial cells respond to LPS when it is presented in combination with soluble CD14 in plasma (55). In this sense, TNFa and IL-ip serve to amplify chemokine production in the lungs by linking cytokine production by myeloid and nonmyeloid cells. 

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