Relapsing poly(peri)chondritis associated with fibrosing alveolar disease and antibodies to pneumocytes type II and clara cells

1989 ◽  
Vol 67 (15) ◽  
pp. 784-789 ◽  
Author(s):  
G. Rauh ◽  
H. Dörfler ◽  
R. Erlinger ◽  
K. G. Riedel ◽  
N. Zöllner
Keyword(s):  
Type Ii ◽  
Clara Cells ◽  
Pneumocytes Type Ii

Differential susceptibilities of isolated hamster lung cell types to amiodarone toxicity

1998 ◽  
Vol 76 (7-8) ◽  
pp. 721-727 ◽  
Author(s):  
M W Bolt ◽  
W J Racz ◽  
J F Brien ◽  
T M Bray ◽  
T E Massey
Keyword(s):  
Alveolar Macrophages ◽  
Gradient Centrifugation ◽  
Cell Types ◽  
Clara Cell ◽  
Blue Dye ◽  
Alveolar Type ◽  
Specific Cell ◽  
Type Ii ◽  
Clara Cells

Treatment of cardiac dysrhythmias with the iodinated benzofuran derivative amiodarone (AM) is limited by pulmonary toxicity. The susceptibilities of different lung cell types of male Golden Syrian hamsters to AM-induced cytotoxicity were investigated in vitro. Bronchoalveolar lavage and protease digestion to release cells, followed by centrifugal elutriation and density gradient centrifugation, resulted in preparations enriched with alveolar macrophages (98%), alveolar type II cells (75-85%), and nonciliated bronchiolar epithelial (Clara) cells (35-50%). Alveolar type II cell and Clara cell preparations demonstrated decreased viability (by 0.5% trypan blue dye exclusion) when incubated with 50 µM AM for 36 h, and all AM-treated cell preparations demonstrated decreased viability when incubated with 100 or 200 µM AM. Based on a viability index ((viability of AM-treated cells ÷ viability of controls) × 100%), the Clara cell fraction was significantly (p < 0.05) more susceptible than all of the other cell types to 50 µM AM. However, AM cytotoxicity was greatest (p < 0.05) in alveolar macrophages following incubation with 100 or 200 µM AM. There was no difference between any of the enriched cell preparations in the amount of drug accumulated following 24 h of incubation with 50 µM AM, whereas alveolar macrophages accumulated the most drug during incubation with 100 µM AM. Thus, the most susceptible cell type was dependent on AM concentration. AM-induced cytotoxicity in specific cell types may initiate processes leading to inflammation and pulmonary fibrosis.Key words: amiodarone, susceptibility, alveolar macrophage, accumulation.

Cell-specific posttranslational processing of the surfactant-associated protein SP-B

1993 ◽  
Vol 264 (3) ◽  
pp. L290-L299 ◽  
Author(s):  
S. Hawgood ◽  
D. Latham ◽  
J. Borchelt ◽  
D. Damm ◽  
T. White ◽  
...  
Keyword(s):  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Cell Types ◽  
Specific Protein ◽  
Precursor Protein ◽  
Type Ii Cells ◽  
Posttranslational Processing ◽  
Type Ii ◽  
Clara Cells ◽  
Ovary Cells

Pulmonary surfactant-associated protein B (SP-B) is a 9-kDa lung-specific protein expressed in alveolar epithelial type II cells and Clara cells. The protein markedly increases the surface activity of phospholipids and is an active component in some surfactants in clinical use. SP-B is produced from a 43-kDa precursor protein by proteolytic cleavage of flanking regions from both the NH2- and COOH-terminal ends of the active protein. In this study we have compared the nature of the posttranslational processing of the SP-B precursor in type II cells and in a heterologous cell line transfected with the SP-B precursor. We found that isolated type II cells produce the 9-kDa form of SP-B from the precursor through a series of intermediates detectable in the cell lysates. In contrast Chinese hamster ovary cells stably transfected with the full-length human SP-B precursor produce the precursor and a 26-kDa intermediate but not the 9-kDa protein. The precursor protein in both cell types is glycosylated with NH2-linked sugars. Our results suggest there is cell specificity in the posttranslational processing of the SP-B precursor.

Localization of a candidate surfactant convertase to type II cells, macrophages, and surfactant subfractions

1999 ◽  
Vol 276 (3) ◽  
pp. L452-L458 ◽  
Author(s):  
Howard Clark ◽  
Lennell Allen ◽  
Erin Collins ◽  
Frederick Barr ◽  
Leland Dobbs ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Alveolar Macrophages ◽  
Pulmonary Surfactant ◽  
Type Ii Cells ◽  
Type Ii ◽  
Clara Cells ◽  
Rat Lung ◽  
Protein Distribution ◽  
Serine Hydrolase ◽  
Surfactant Metabolism

Pulmonary surfactant exists in the alveolus in several distinct subtypes that differ in their morphology, composition, and surface activity. Experiments by others have implicated a serine hydrolase in the production of the inactive small vesicular subtype of surfactant (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222–230, 1990). Our laboratory recently identified this enzyme in the rat as the serine carboxylesterase ES-2 [F. Barr, H. Clark, and S. Hawgood. Am. J. Physiol. 274 ( Lung Cell. Mol. Physiol. 18): L404–L410, 1998]. In the present study, we determined the cellular sites of expression of ES-2 in rat lung using a digoxygenin-labeled ES-2 riboprobe. ES-2 mRNA was localized to type II cells and alveolar macrophages but not to Clara cells. Using a specific ES-2 antibody, we determined the protein distribution of ES-2 in the lung by immunohistochemistry, and it was found to be consistent with the sites of mRNA expression. Most of the ES-2 in rat bronchoalveolar lavage is in the surfactant-depleted supernatant, but ES-2 was also consistently localized to the small vesicular surfactant subfraction presumed to form as a consequence of conversion activity. These results are consistent with a role for endogenous lung ES-2 in surfactant metabolism.

An improved method for the isolation of type II and clara cells from mice

1995 ◽  
Vol 31 (5) ◽  
pp. 361-366 ◽  
Author(s):  
Steven A. Belinsky ◽  
John F. Lechner ◽  
Neil F. Johnson
Keyword(s):  
Type Ii ◽  
Clara Cells ◽  
Improved Method

scholarly journals TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human surfactant protein-A2 promoter activity

2008 ◽  
Vol 295 (2) ◽  
pp. L264-L271 ◽  
Author(s):  
Dongyuan Liu ◽  
Ming Yi ◽  
Margaret Smith ◽  
Carole R. Mendelson
Keyword(s):  
Hormonal Regulation ◽  
Promoter Activity ◽  
Interleukin 1 ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Type Ii ◽  
Clara Cells ◽  
T Box ◽  
E Box ◽  
Specific Regulation

Expression of the human surfactant protein-A2 ( hSP-A2) gene is lung specific, occurs in type II and Clara cells, and is developmentally and hormonally regulated in fetal lung. Using transfected human fetal type II cells, we previously observed that ∼300 bp of 5′-flanking DNA mediated cAMP and interleukin-1 (IL-1) stimulation and dexamethasone (Dex) inhibition of hSP-A2 promoter activity. This region contains response elements for estrogen-related receptor α element (ERRE, −241 bp), thyroid transcription factor (TTF)-1/Nkx2.1 (TTF-binding protein, −171 bp), upstream stimulatory factor 1/2 (E-box, −80 bp), and stimulatory protein (Sp) 1 (G/T-box, −62 bp), which are essential for basal and cAMP induction of hSP-A2 expression. To define genomic regions necessary for developmental, hormonal, and tissue-specific regulation of hSP-A2 expression in vivo, we analyzed transgenic mice carrying hGH reporter genes comprised of 313 bp of hSP-A2 gene 5′-flanking DNA ± mutation in the TBE or 175 bp of 5′-flanking DNA, containing TBE, E-box and G/T-box, but lacking ERRE. Transgenes containing 313 or 175 bp of hSP-A2 5′-flanking DNA were expressed in a lung cell-specific manner and developmentally regulated in concert with the endogenous mouse SP-A gene. In cultured lung explants from hSP-A− 313 :hGH transgenic fetal mice, cAMP and IL-1 induced and Dex inhibited transgene expression. However, the 175-bp hSP-A2 genomic region was insufficient to mediate hormonal regulation of hSP-A2 promoter activity. The finding that expression of the hSP-A− 313TBEmut :hGH transgene was essentially undetectable in fetal lung and was not hormonally regulated in transgenic fetal lung explants underscores the critical importance of the TBE in lung cell-specific, developmental, and hormonal regulation of hSP-A2 gene expression.

scholarly journals C/EBPα is required for pulmonary cytoprotection during hyperoxia

2009 ◽  
Vol 297 (2) ◽  
pp. L286-L298 ◽  
Author(s):  
Yan Xu ◽  
Chika Saegusa ◽  
Angelica Schehr ◽  
Shawn Grant ◽  
Jeffrey A. Whitsett ◽  
...  
Keyword(s):  
Protein Biosynthesis ◽  
Critical Role ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Lung Mechanics ◽  
Type Ii Cells ◽  
Type Ii ◽  
Clara Cells ◽  
Lung Maturation ◽  
Surfactant Lipid

A number of transcriptional pathways regulating fetal lung development are active during repair of the injured lung. We hypothesized that C/EBPα, a transcription factor critical for lung maturation, plays a role in protection of the alveolar epithelium following hyperoxic injury of the mature lung. Transgenic CebpαΔ/Δmice, in which Cebpα was conditionally deleted from Clara cells and type II cells after birth, were developed. While no pulmonary abnormalities were observed in the CebpαΔ/Δmice (7–8 wk old) under normal conditions, the mice were highly susceptible to hyperoxia. CebpαΔ/Δmice died within 4 days of exposure to 95% oxygen in association with severe lung inflammation, altered maturation of surfactant protein B and C, decreased surfactant lipid secretion, and abnormal lung mechanics at a time when all control mice survived. mRNA microarray analysis of isolated type II cells at 0, 2, and 24 h of hyperoxia demonstrated the reduced expression of number of genes regulating surfactant lipid and protein homeostasis, including Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes influencing cell signaling or immune responses were induced in the lungs of CebpαΔ/Δmice. C/EBPα was required for the regulation of genes associated with surfactant lipid homeostasis, surfactant protein biosynthesis, processing and transport, defense response to stress, and cell redox homeostasis during exposure to hyperoxia. While C/EBPα did not play a critical role in postnatal pulmonary function under normal conditions, C/EBPα mediated protection of the lung during acute lung injury induced by hyperoxia.

Brief 95% O2 exposure effects on surfactant protein and mRNA in rat alveolar and bronchiolar epithelium

1999 ◽  
Vol 276 (6) ◽  
pp. L999-L1009 ◽  
Author(s):  
Thomas F. Allred ◽  
Robert R. Mercer ◽  
Ronald F. Thomas ◽  
Hui Deng ◽  
Richard L. Auten
Keyword(s):  
Northern Blot ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Male Rats ◽  
Type Ii ◽  
Clara Cells ◽  
Fixed Tissue ◽  
Bronchiolar Epithelium ◽  
Alveolar Stability

In acute lung injury, a disturbed surfactant system may impair gas exchange. Previous evaluations of hyperoxia effects on surfactant proteins (SPs) followed exposures >1–2 days. To evaluate the effects of brief exposure to hyperoxia on the SP system, we exposed adult male rats to 95% O2 or air for 12, 36, and 60 h. SP-A, -B, and -C mRNAs were analyzed by Northern blot and semiquantitative in situ hybridization (ISH). SP-A and -B were analyzed in whole lung homogenates, lung lavage fluid, and fixed tissue by semiquantitative immunohistochemistry (IHC). All SP mRNAs were diminished at 12 h and rose to or exceeded control by 60 h as determined by Northern blot and ISH. These effects were seen mainly in the intensity of ISH signal per cell in both type II and bronchiolar epithelial (Clara) cells and to a lesser extent on numbers of positively labeled cells. SP-B declined to 50% of control in lavage at 12 h, but no changes in total lung SP-A and -B were seen. The number of SP-A positively labeled cells did not change, but SP-A label intensity measured by IHC in type II cells showed parallel results to Northern blots and ISH. The response of SP-A in Clara cells was similar. SP-B immunolabeling intensity rose in both type II and Clara cells throughout the exposure. SP-C ISH intensity fell at 12 h and was increased to two times control by 60 h of hyperoxia. Sharp declines in SP expression occurred by 12 h of 95% O2 and may affect local alveolar stability.

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