Cytokines and Alveolar Type II Cells
Jason Kelley in Cytokines of the Lung, 2022
Alveolar type II cells synthesize, store, and secrete the surface active material that lines the alveolar space and stabilizes the alveolus at low lung volumes by decreasing the surface tension of the alveolar lining fluid. This material is composed of lipids, proteins, and carbohydrates. Approximately 70–80% of the phospholipid in surfactant is phosphatidylcholine, and phosphatidylglycerol is the second major phospholipid component (Rooney, 1985). Dipalmitoylphosphatidylcholine composes 50–60% of the phosphatidyl-choline and is thought to be the major phospholipid species responsible for the stability of the surface active material lining the alveolar space (Wright and Clements, 1987; Clements and Tierney, 1965). The alveolar type II cell is the major source of surface active material within the lung. The biosynthetic pathways, metabolism, secretion, and uptake of surfactant by alveolar type II cells have been extensively reviewed (Rooney, 1985; Wright and Clements, 1987; Wright, 1990; Chander and Fisher, 1990; Mendelson and Boggaram, 1990). This chapter will focus on the effect of cytokines and hormones on surfactant biosynthesis and secretion by alveolar type II cells (Table 1). Pharmacologic agents used to stimulate surfactant synthesis or secretion will not be reviewed.
Overview of lung surfactant and respiratory distress syndrome
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
PS is an elegant and complex mixture of 90% phospholipids and 10% surface-active protein. There are four known lung surfactant proteins, that is, surfactant-specific proteins: SP-A, SP-B, SP-C, and SP-D. Of the phospholipid content, 55%–60% is dipalmitoylphosphatidylcholine (DPPC), in addition to the anionic phospholipid palmitoyloleoylphosphatidylglycerol (POPG), and palmitoyloleoylphosphatidylcholine (POPC), which are all important in the spreading mechanisms (1,2) and stability. SP-A and SP-D proteins depend on calcium and are large hydrophilic proteins. SP-A and SP-D proteins are critical in pulmonary immunity, alveolar macrophage stimulation, and regulating pulmonary immune response. In contrast to SP-A and SP-D proteins, SP-B and SP-C proteins are hydrophobic proteins and are relatively smaller in size. SP-B and SP-C proteins are needed in lung surfactant spreading mechanisms, lung surfactant stability, and the normal function of lung surfactant.
Membrane-Splitting Analyses of Membrane-Spanning Proteins
Sek Wen Hui in Freeze-Fracture Studies of Membranes, 1989
The transbilayer distribution of tritiated dipalmitoylphosphatidylcholine (3H-DPPC) was also recently evaluated by membrane splitting.116 As a control, red cells were incubated with aqueous dispersions of 3H-DPPC for 4 h at 37°C, cooled to 0 to 4°C, and thoroughly washed prior to monolayer formation. DBLAMS analysis revealed a significantly different asymmetry for DPPC relative to cholesterol: about 80% partitioned with the extracellular leaflet vs. 20% with the inner leaflet. Similar values were determined for incubations ranging up to 24 h. Thus the asymmetry probably represents the equilibrium distribution of 3H-DPPC (Figure 2B, B’). Quantification of 3H-DPPC distribution demonstrated that DBLAMS techniques were suitable for examining radiolabeled phospholipids as well as the neutral lipid cholesterol. In addition, the DPPC studies validated qualitative and quantitative applications of the DBLAMS methods, since other biochemical and biophysical assays had demonstrated a similar transbilayer asymmetry of the choline-containing phospholipids of the red cell membrane, including sphingomyelin and phosphatidylcholine.14,15
Fabrication of versatile targeted lipopolymersomes for improved camptothecin efficacy against colon adenocarcinoma in vitro and in vivo
Published in Expert Opinion on Drug Delivery, 2021
Mahsa Zahiri, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, Mona Alibolandi
Camptothecin was obtained from Tocris Bioscience Co., Ltd. (Ellisville, USA). Dipalmitoylphosphatidylcholine (DPPC) was obtained from Avanti Polar Lipids (Alabama, USA). Methoxy poly-(ethylene glycol) (Mw = 2000 Da), 1,1ʹ-dioctadecyl-3,3,3ʹ,3ʹ-tetramethylindocarbocyanine perchlorate (DiI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were obtained from Sigma–Aldrich (Schnelldorf, Germany). Poly(L-lactide)3000-PEGm2000 and Poly(L-lactide)3000-PEG-MAL2000 were prepared from Nano Soft Polymers (Winston-Salem, USA). Roswell Park Memorial Institute-1640 (RPMI-1640) medium, penicillin-streptomycin solution, trypsin and fetal bovine serum (FBS) were acquired from GIBCO (Darmstadt, Germany). C26 (murine colon carcinoma cells), HT29 (human colon adenocarcinoma), and CHO (Chinese hamster ovary) cell lines were supplied by Pasteur Institute of Iran (Tehran, Iran). Other solvents and chemical reagents applied in this project were procured from Merck & Co (Darmstadt, Germany). All chemicals with analytical grade were utilized without further purification. The AS1411 aptamer [SH-5-(GGTGGTGGTGGTTGTGGTGGTGGTGG)-3′] was acquired from Microsynth AG (Balgach, Switzerland).
Simulation of respiratory tract lining fluid for in vitro dissolution study
Published in Expert Opinion on Drug Delivery, 2021
Rakesh Bastola, Paul M. Young, Shyamal C. Das
Lung surfactant (LS) is a surface-active lipid–protein material [32]. Around 92% of LS is lipid and 8% is surfactant protein (SP) by mass [33]. Lipids include fully saturated dipalmitoylphosphatidylcholine (DPPC) as the major phospholipid. In addition, LS contains unsaturated phosphatidylcholine (PC), anionic phosphatidylglycerol (PG) and phosphatidylinositol (PI) as well as neutral lipids such as cholesterol (also being the most prominent) [33]. Around 8% of the total LS mass contains four specific SPs, and they are categorized into two groups. The larger hydrophilic surfactant protein A (SP-A) and surfactant protein D (SP-D) come under the collectin protein family. They are basically responsible for innate immunity. The smaller hydrophobic surfactant protein B (SP-B) and surfactant protein C (SP-C) are inserted in and between the LS-associated phospholipid layers. They are necessary for LS interfacial adsorption and are responsible for the safeguarding of surfactant film stability during consecutive breathing cycles [33].
Furin-responsive triterpenine-based liposomal complex enhances anticervical cancer therapy through size modulation
Published in Drug Delivery, 2020
Yunyan Chen, Mengfei Guo, Ding Qu, Yuping Liu, Jian Guo, Yan Chen
GRVRRSC (G: glycine; R: arginine; V: valine; S: serine; C: cysteine) was provided by GL Biochem Co., Ltd. (Shanghai, China). MonomethoxyPEG (mPEG) was provided by Sigma-Aldrich (St. Louis, MO). 4-Dimethylaminopyridine (DMAP), 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindodicarbo cyanine iodide (DiD) and Triethylamine (TEA) were all provided by Aladdin Co., Ltd. (Shanghai, China). Octadecanol, succinic anhydride, maleic anhydride, and tripterine (purity >98.0%) were all purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Coix seed oil (extracted by carbon dioxide supercritical technology, purity >85%). RH 40 and PEG 400 were purchased from BASF Co., Ltd. (Ludwigshafen, Germany). Dipalmitoylphosphatidylcholine (DPPC), stearoyllysophosphocholine (S-lysoPC), and Distearoylphosphoethanolamine-PEG2000 (DSPE-MPEG2k) were provided by A.V.T Co., Ltd. (purity > 98.0%, China). Double-distilled water was purified via Milli Q purification system (Merck Millipore). All other reagents used were of analytical grade.
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