Measurement of Protein Permeability and Fluid Transport of Human Alveolar Epithelial Type II Cells Under Pathological Conditions

Author(s):  
Xiaohui Fang ◽  
Michael A. Matthay
2000 ◽  
Vol 279 (1) ◽  
pp. L127-L135 ◽  
Author(s):  
David M. Guidot ◽  
Katharina Modelska ◽  
Manuel Lois ◽  
Lucky Jain ◽  
I. Marc Moss ◽  
...  

We determined that rats fed a liquid diet containing ethanol (36% of calories) for 6 wk had decreased ( P < 0.05) net vectorial fluid transport and increased ( P < 0.05) bidirectional protein permeability across the alveolar epithelium in vivo compared with rats fed a control diet. However, both groups increased ( P < 0.05) fluid transport in response to epinephrine (10−5 M) stimulation, indicating that transcellular sodium transport was intact. In parallel, type II cells isolated from ethanol-fed rats and cultured for 8 days formed a more permeable monolayer as reflected by increased ( P < 0.05) leak of [14C]inulin. However, type II cells from ethanol-fed rats had more sodium-permeant channels in their apical membranes than type II cells isolated from control-fed rats, consistent with the preserved response to epinephrine in vivo. Finally, the alveolar epithelium of ethanol-fed rats supplemented withl-2-oxothiaxolidine-4-carboxylate (Procysteine), a glutathione precursor, had the same ( P < 0.05) net vectorial fluid transport and bidirectional protein permeability in vivo and permeability to [14C]inulin in vitro as control-fed rats. We conclude that chronic ethanol ingestion via glutathione deficiency increases alveolar epithelial intercellular permeability and, despite preserved or even enhanced transcellular sodium transport, renders the alveolar epithelium susceptible to acute edematous injury.


2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Xiaohui Fang ◽  
Jae‐Woo Lee ◽  
Arne Neyrink ◽  
Linda W Gonzales ◽  
Philip L Ballard ◽  
...  

2007 ◽  
Vol 282 (33) ◽  
pp. 24109-24119 ◽  
Author(s):  
Jae W. Lee ◽  
Xiaohui Fang ◽  
Gregory Dolganov ◽  
Richard D. Fremont ◽  
Julie A. Bastarache ◽  
...  

1998 ◽  
Vol 275 (3) ◽  
pp. L478-L490 ◽  
Author(s):  
Hans G. Folkesson ◽  
Gerard Nitenberg ◽  
Bonnie L. Oliver ◽  
Christian Jayr ◽  
Kurt H. Albertine ◽  
...  

Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). An isosmolar Ringer lactate solution with 5% bovine serum albumin and125I-labeled albumin as the alveolar protein tracer was instilled into the right lung; the rats were then studied for either 1 or 4 h. Alveolar fluid clearance was increased in bleomycin-injured rats by 110% over 1 h and by 75% over 4 h compared with control rats ( P < 0.05). The increase in alveolar fluid clearance was partially inhibited by amiloride (10−3 M). Alveolar fluid clearance decreased toward normal levels in rats that were studied 60 days after bleomycin instillation. Remarkably, the measured increase in net alveolar fluid clearance occurred in the presence of a significant increase in alveolar epithelial permeability to protein. Moreover, the increase in alveolar epithelial fluid clearance occurred even though the mRNA for the α-subunit of the epithelial sodium channel was decreased in alveolar epithelial type II cells isolated from these rats. In addition,22Na uptake by isolated alveolar epithelial type II cells from rats treated with bleomycin demonstrated a 52% decrease in uptake compared with type II cells from control rats. Morphological results demonstrated a significant hyperplasia of alveolar type II epithelial cells 10 days after bleomycin injury. Thus, these results provide evidence that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the transport capacity of the alveolar epithelium, even though the expression of epithelial sodium channels is reduced and the uptake of22Na per cell is also reduced. These results may have clinical relevance for the resolution of alveolar edema in the subacute phase of lung injury.


1999 ◽  
Vol 87 (5) ◽  
pp. 1852-1860 ◽  
Author(s):  
Yibing Wang ◽  
Hans G. Folkesson ◽  
Christian Jayr ◽  
Lorraine B. Ware ◽  
Michael A. Matthay

Although keratinocyte growth factor (KGF) protects against experimental acute lung injury, the mechanisms for the protective effect are incompletely understood. Therefore, the time-dependent effects of KGF on alveolar epithelial fluid transport were studied in rats 48–240 h after intratracheal administration of KGF (5 mg/kg). There was a marked proliferative response to KGF, measured both by in vivo bromodeoxyuridine staining and by staining with an antibody to a type II cell antigen. In controls, alveolar liquid clearance (ALC) was 23 ± 3%/h. After KGF pretreatment, ALC was significantly increased to 30 ± 2%/h at 48 h, to 39 ± 2%/h at 72 h, and to 36 ± 3%/h at 120 h compared with controls ( P < 0.05). By 240 h, ALC had returned to near-control levels (26 ± 2%/h). The increase in ALC was explained primarily by the proliferation of alveolar type II cells, since there was a good correlation between the number of alveolar type II cells and the increase in ALC ( r = 0.92, P = 0.02). The fraction of ALC inhibited by amiloride was similar in control rats (33%) as in 72-h KGF-pretreated rats (38%), indicating that there was probably no major change in the apical pathways for Na uptake in the KGF-pretreated rats at this time point. However, more rapid ALC at 120 h, compared with 48 h after KGF treatment, may be explained by greater maturation of α-epithelial Na channel, since its expression was greater at 120 than at 48 h, whereas the number of type II cells was the same at these two time points. β-Adrenergic stimulation with terbutaline 72 h after KGF pretreatment further increased ALC to 50 ± 7%/h ( P < 0.5). In summary, KGF induced a sustained increase over 120 h in the fluid transport capacity of the alveolar epithelium. This impressive upregulation in fluid transport was further enhanced with β-adrenergic agonist therapy, thus providing evidence that two different treatments can simultaneously increase the fluid transport capacity of the alveolar epithelium.


2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Nili Jin ◽  
Narasaiah Kolliputi ◽  
Deming Gou ◽  
Tingting Weng ◽  
Lin Liu

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Arne Pieter Neyrinck ◽  
Jae‐Woo Lee ◽  
Xiaohui Fang ◽  
Naveen Gupta ◽  
Michael A Matthay

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