Pneumocytes surfactants

Phospholipid that is the major component of Tung surfactant, and the syndrome caused by its deficiency Dipalmitoylphosphatidylcholine (DPPC, also called dipalmitoyllecithin, DPPL) is the major lipid component of lung surfactant. It is made and secreted by type II granular pneu-mocytes. Insufficient surfactant production causes respiratory distress syndrome, which can occur in preterm infants or adults whose surfactant-producing pneumocytes have been damaged or destroyed. 

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]. 

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. 

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... 

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... 

After internahsation into isolated rat type II pneumocytes, SP-A and Hpid were taken up via the coated-pit pathway and resided in a common compartment, positive for the early endosomal marker EEAl but negative for the lamellar body marker 3C9 (WissEL et al. 2001). SP-A then recycled rapidly to the cell surface via Rab4-associated recycHng vesicles. Internalised lipid was transported toward a Rab7-, CD63-, 3C9-positive compartment, i.e., lamellar bodies. Inhibition of calmodulin led to inhibition of uptake and transport out of the EEAl-positive endosome and thus of resecretion of both components. Inhibition of intravesicular acidification (bafilomycin Ai) led to decreased uptake of both surfactant components. It inhibited transport out of early endosomes for lipid only, not for SP-A. 

Surfactant protein B (SP-B), an 8 kDa hydrophobic protein essential for surfactant function, is produced from the intracellular processing of the 381 amino acid residues, 40 kDa preprotein SP-B within the type II pneumocytes. 

Surfactant protein C (SP-C) is synthesised by type II pneumocytes as a 21 kDa propeptide which is proteolytically processed in subcellular compartments distal to the trans-Golgi network to yield the 35 residue mature form. 

Surfactant convertase, a diisopropylfluorophos-phate (DFP)-binding and DFP inhibitable carboxyl-esterase (Gross et al. 1997) of 70 kDa (reduced), is required for conversion of heavy density (tubular myelin) to fight density (small vesicle) subtypes of surfactant. Carboxylesterase ES-2 mRNA was localised to type II pneumocytes and alveolar macrophages but not to Clara cells (Clark et al. 1997). Lamellar bodies contain both glycosylated (70 kDa)... 

Arg ]-vasopressin stimulated surfactant secretion in primary cultures of rat type 2 pneumocytes independently of adenosine 3 ,5 -cyclic monophosphate (Brown and Wood 1989). A 50% loss of tritiated phosphatidyhnsositol 4,5-biphosphate (PIP2) occurred from cells prelabeled with myo[ H]inositol within 15 s (Brown and Chen 1990). Consistent with vasopressin-induced PIP2 hydrolysis the two breakdown products, 1,2-diacylglycerol and inositol 1,4,5-triphosphate, was observed. Vasopressin stimulated protein kinase C activity twofold over the basal activity of 0.7410.07 nM/min x mg protein. The [Arg ]-vasopressin antagonist, 1-deamino-8-D-arginine vasopressin, inhibited [Arg ]-vasopressin activation of protein kinase C. 

The size of the type II pneumocytes was conspicuously increased by about 30 % in Lewis rats treated with 300 mg clofibrate/kg body weight x day by in-traperitoneal injections for 7 days (Fringes and Reith 1988). Peroxisomes proliferated and there was an increase in the number of surfactant-rich lamellar bodies (Fringes et al. 1988). 

Pentoxifylline antagonised the inhibition of surfactant synthesis induced by TNF-a in type II pneumocytes isolated from human cadaveric multiple organ donors and lung-cancer patients (Balibrea-Cantero et al. 1994). 

Another important natural protein surfactant in mammalian are lung surfactants, which are secreted by type II pneumocytes and reduce surface tension at the air-water interface of distal airways and the alveoli of lungs, thereby decreasing the work of breathing and the tendency for alveoli to collapse at low lung volumes. The components of lung surfactants as well as the structure and functions of surfactant proteins have been precisely reviewed recently [62]. 

Serum lactate dehydrogenase (LDH) is elevated in 80% of patients with iPAP (1,4,5,11,32). Concentrations of carcinoembryonic antigen (CEA) (5), cytoker-atin (11), Kreb von den Lungen-6 (KL-6), a mucin-like protein secreted by type 11 pneumocytes (35-37), and surfactant proteins-A (SP-A) and SP-D (37 0) are elevated in serum and BALE in iPAP. However, these various laboratory findings are not specific for PAP (5,40). 

Chevalier G, Collet AJ. In vivo incorporation of choline- H, leucine- H and galac-tose- H in alveolar type II pneumocytes in relation to surfactant synthesis. A quantitative radioautographic study in mouse by electron microscopy. Anat Rec 1972 174 289-310. 

Uhal BD, Etter MD. Type-II pneumocyte hypertrophy without activation of surfactant biosynthesis after partial pneumonectomy. Am J Physiol 1993 264 L153-L159. 

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