Natural Protection from Apoptosis by Surfactant Protein A in Type II Pneumocytes

2001 ◽  
Vol 263 (2) ◽  
pp. 183-192 ◽  
Author(s):  
Martyn K. White ◽  
Vijayabhasker Baireddy ◽  
David S. Strayer
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Natural Protection

scholarly journals Role of the PI3-kinase signaling pathway in trafficking of the surfactant protein A receptor P63 (CKAP4) on type II pneumocytes

2010 ◽  
Vol 299 (6) ◽  
pp. L794-L807 ◽  
Author(s):  
Altaf S. Kazi ◽  
Jian-Qin Tao ◽  
Sheldon I. Feinstein ◽  
Li Zhang ◽  
Aron B. Fisher ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Protein A ◽  
Surfactant Protein ◽  
Pi3 Kinase ◽  
Surfactant Protein A ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Kinase Signaling Pathway ◽  
Stimulation Of

Surfactant protein A (SP-A) plays an important role in the maintenance of lung lipid homeostasis. Previously, an SP-A receptor, P63 (CKAP4), on type II pneumocyte plasma membranes (PM) was identified by chemical cross-linking techniques. An antibody to P63 blocked the specific binding of SP-A to pneumocytes and the ability of SP-A to regulate surfactant secretion. The current report shows that another biological activity of SP-A, the stimulation of surfactant uptake by pneumocytes, is inhibited by P63 antibody. cAMP exposure resulted in enrichment of P63 on the cell surface as shown by stimulation of SP-A binding, enhanced association of labeled P63 antibody with type II cells, and promotion of SP-A-mediated liposome uptake, all of which were inhibited by competing P63 antibody. Incubation of A549 and type II cells with SP-A also increased P63 localization on the PM. The phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway was explored as a mechanism for the transport of this endoplasmic reticulum (ER)-resident protein to the PM. Treatment with LY-294002, an inhibitor of the PI3-kinase pathway, prevented the SP-A-induced PM enrichment of P63. Exposure of pneumocytes to SP-A or cAMP activated Akt (PKB). Blocking either PI3-kinase or Akt altered SP-A-mediated lipid turnover. The data demonstrate an important role for the PI3-kinase-Akt pathway in intracellular transport of P63. The results add to the growing body of evidence that P63 is critical for SP-A receptor-mediated interactions with type II pneumocytes and the resultant regulation of surfactant turnover.

scholarly journals Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytes

2008 ◽  
Vol 295 (4) ◽  
pp. L658-L669 ◽  
Author(s):  
Sandra R. Bates ◽  
Altaf S. Kazi ◽  
Jian-Qin Tao ◽  
Kevin J. Yu ◽  
Daniel S. Gonder ◽  
...  
Keyword(s):  
Specific Binding ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii Cells ◽  
Type Ii ◽  
Calcium Dependent ◽  
Type Ii Pneumocytes ◽  
Surfactant Secretion

We have recently described a putative receptor for lung surfactant protein-A (SP-A) on rat type II pneumocytes. The receptor, P63, is a 63-kDa type II transmembrane protein. Coincubation of type II cells with P63 antibody (Ab) reversed the inhibitory effect of SP-A on secretagogue-stimulated surfactant secretion from type II cells. To further characterize SP-A interactions with P63, we expressed recombinant P63 protein in Escherichia coli and generated antibodies to P63. Immunogold electron microscopy confirmed endoplasmic reticulum and plasma membrane localization of P63 in type II cells with prominent labeling of microvilli. Binding characteristics of iodinated SP-A to type II cells in the presence of P63 Ab were determined. Binding (4°C, 1 h) of 125I-SP-A to type II cells demonstrated both specific (calcium-dependent) and nonspecific (calcium-independent) components. Ab to P63 protein blocked the specific binding of 125I-SP-A to type II cells and did not change the nonspecific SP-A association. A549 cells, a pneumocyte model cell line, expressed substantial levels of P63 and demonstrated specific binding of 125I-SP-A that was inhibited by the P63 Ab. The secretagogue (cAMP)-stimulated increase in calcium-dependent binding of SP-A to type II cells was blocked by the presence of P63 Ab. Transfection of type II cells with small interfering RNA to P63 reduced P63 protein expression, attenuated P63-specific SP-A binding, and reversed the ability of SP-A to prevent surfactant secretion from the cells. Our results further substantiate the role of P63 as an SP-A receptor protein localized on the surface of lung type II cells.

Altered Surfactant Protein-A Expression in Type II Pneumocytes in COPD

CHEST Journal ◽  
2010 ◽  
Vol 137 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Eleni M. Vlachaki ◽  
Anastassios V. Koutsopoulos ◽  
Nikolaos Tzanakis ◽  
Eirini Neofytou ◽  
Marianna Siganaki ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii ◽  
Type Ii Pneumocytes

scholarly journals Forward transport of the receptor P63 is necessary for secretagogue‐enhanced surfactant protein‐A (SP‐A) binding to type II pneumocytes

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Sandra R. Bates ◽  
Altaf S. Kazi ◽  
Jian‐Qin Tao ◽  
Sheldon I. Feinstein ◽  
Aron B. Fisher
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii ◽  
Type Ii Pneumocytes

Surfactant Protein A Stimulates Release of Neutrophil Chemotactic Factors by Alveolar Type II Pneumocytes

Lung ◽  
2010 ◽  
Vol 188 (6) ◽  
pp. 491-497 ◽  
Author(s):  
Mitchell J. Kresch ◽  
Mitchell Block ◽  
Mohammed R. Karim ◽  
Li Zhu ◽  
Naveed Hussain ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Chemotactic Factors

Secretion of surfactant protein A from rat type II pneumocytes

1993 ◽  
Vol 265 (6) ◽  
pp. L586-L590 ◽  
Author(s):  
S. A. Rooney ◽  
L. I. Gobran ◽  
T. M. Umstead ◽  
D. S. Phelps
Keyword(s):  
Primary Cultures ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii ◽  
Isolated Cells ◽  
Adult Rats ◽  
Pharmacological Agents ◽  
Type Ii Pneumocytes ◽  
Phosphatidylcholine Secretion

Secretion of surfactant phosphatidylcholine has been extensively studied and there is evidence that it is a regulated process that can be influenced by a variety of physiological factors and pharmacological agents. In contrast, secretion of the major surfactant protein, surfactant protein A (SP-A), has been investigated to much lesser extent. It is not known whether SP-A secretion is constitutive or regulated and, if regulated, whether its regulation is similar to that of phosphatidylcholine. To address those questions we measured SP-A secretion in primary cultures of type II pneumocytes under conditions identical to those used to study phosphatidylcholine secretion. Freshly isolated cells from adult rats were cultured overnight, washed, and then incubated in fresh medium in the presence and absence of surfactant phospholipid secretagogues. As previously reported for phosphatidylcholine, SP-A secretion was linear with time for up to 4 h. However, the rate of SP-A secretion, approximately 6% of total SP-A (cells+medium) released into the medium per hour, was more than sixfold greater than that of the lipid. Although freshly isolated cells contained 70% more SP-A than cells that were cultured overnight, the rate of SP-A secretion was not significantly different. Secretion of SP-A by freshly isolated or cultured type II cells was not increased by a combination of ATP, terbutaline, the adenosine A2 receptor agonist 5'(N-ethylcarboxyamido)adenosine, 12-O-tetradecanoylphorbol-13-acetate, and ionomycin at concentrations that optimally stimulated phosphatidylcholine secretion. We conclude that secretion of the major lipid and protein components of surfactant are independently regulated.

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