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Gene Review

SFTPA1  -  surfactant protein A1

Ovis aries

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Disease relevance of SP-A

  • Mild hypoxia for 48 h resulted in an increase in plasma cortisol that was more pronounced at later gestation, and in these animals, there was a twofold increase in SP-A mRNA [1].
  • At approximately 2 wk after preterm birth, SP-A and SP-B, but not SP-C, mRNA levels were significantly reduced in preterm lambs compared with term controls, but these differences did not persist at 2 and 6 wk PNA [2].
  • To determine the timing of these changes, the objective of the present study was to characterize the effect of increased pulmonary blood flow and pulmonary hypertension on SP-A, -B, and -C gene expressions and protein contents within the first week of life [3].
  • Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung [4].
  • Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A) [5].

High impact information on SP-A

  • After 6 h of ventilation, cell numbers in the alveolar wash were 4.9 times higher in SP-A + SP-C-surfactant-treated animals [6].
  • The present study identifies an unanticipated role of SP-A in neutrophil recruitment in the lungs of preterm lambs [6].
  • The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown [7].
  • No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170 [7].
  • In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene [7].

Chemical compound and disease context of SP-A

  • Although surfactant secreted early by the fetus into alveolar spaces contained normal levels of BAL SP-A and BAL SP-B, the low levels of BAL PC and low lung tissue stores of SP-B indicate that these experimental lambs may experience respiratory insufficiency soon after birth [8].

Biological context of SP-A


Anatomical context of SP-A

  • Furthermore, uptake of C1q-coated beads was enhanced when either beads or alveolar macrophages were preincubated with SP-A [10].
  • It inhibited transport out of early endosomes for lipid only, not for SP-A [14].
  • Endocytosed SP-A and surfactant lipids are sorted to different organelles in rat type II pneumocytes [14].
  • De novo synthesized SP-A is secreted independently of lamellar bodies and may associate with surfactant lipids during the formation of tubular myelin [12].
  • Defensins and surfactant protein A (SP-A) and SP-D are antimicrobial components of the pulmonary innate immune system [15].

Associations of SP-A with chemical compounds

  • Alveolar or lung tissue, saturated phosphatidylcholine, or alveolar SP-A pool sizes did not change with hormone treatment at 135 d gestation [16].
  • As estimated by subcellular fractionation, at this time point, 23% of the internalized SP-A and 45% of internalized lipid were localized within light (<0.38 M sucrose) fractions, which contain lamellar bodies and are positive for EEA1 [11].
  • Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice [17].
  • Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice [17].

Other interactions of SP-A

  • Following the release of a TO, SP-A, SP-B and SP-C mRNA levels were closely and inversely related to the volume of lung liquid [18].

Analytical, diagnostic and therapeutic context of SP-A

  • Although the steady-state level of transcripts of surfactant protein (SP)-A and SP-B was not found to be changed at the time of death, semiquantitative Western blot analysis revealed elevated SP-A and SP-B protein contents three- and twofold, respectively [19].
  • The purpose of the present study was to utilize our animal model to determine the effects on the expression of surfactant proteins A (SP-A), B (SP-B), and C (SP-C) [20].
  • At 138 days g.a., lungs were harvested and the following parameters were measured: SP-A, -B, and -C mRNA expression (Northern blot), SP-A and -B expression (Western blot), and AE2 cell density (immunohistochemistry) [21].
  • In this study we measured in lung lavage surfactant total phospholipids and surfactant-associated proteins A and B (SP-A, SP-B) [22].
  • Protein levels of SP-A in lung homogenates detected by quantitative-competitive enzyme-linked immunosorbent assay and protein antigen of SP-A detected by IHC were not altered [15].


  1. Ovine surfactant protein cDNAs: use in studies on fetal lung growth and maturation after prolonged hypoxemia. Braems, G.A., Yao, L.J., Inchley, K., Brickenden, A., Han, V.K., Grolla, A., Challis, J.R., Possmayer, F. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  2. Alveolar epithelial cell differentiation and surfactant protein expression after mild preterm birth in sheep. Sozo, F., Wallace, M.J., Hanna, M.R., Flecknoe, S.J., Cock, M.L., Maritz, G.S., Harding, R., Hooper, S.B. Pediatr. Res. (2006) [Pubmed]
  3. Increased pulmonary blood flow does not alter surfactant protein gene expression in lambs within the first week of life. Lee, J.W., Ovadia, B., Azakie, A., Salas, S., Goerke, J., Fineman, J.R., Gutierrez, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  4. Injury responses to different surfactants in ventilated premature lamb lungs. Ikegami, M., Jobe, A.H. Pediatr. Res. (2002) [Pubmed]
  5. Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A). Lesur, O., Bouhadiba, T., Melloni, B., Cantin, A., Whitsett, J.A., Bégin, R. International journal of experimental pathology. (1995) [Pubmed]
  6. Surfactant protein A recruits neutrophils into the lungs of ventilated preterm lambs. Kramer, B.W., Jobe, A.H., Bachurski, C.J., Ikegami, M. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
  7. Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein A gene. DeMartini, J.C., Bishop, J.V., Allen, T.E., Jassim, F.A., Sharp, J.M., de las Heras, M., Voelker, D.R., Carlson, J.O. J. Virol. (2001) [Pubmed]
  8. Surfactant levels after reversible tracheal occlusion and prenatal steroids in experimental diaphragmatic hernia. Bratu, I., Flageole, H., Laberge, J.M., Possmayer, F., Harbottle, R., Kay, S., Khalife, S., Piedboeuf, B. J. Pediatr. Surg. (2001) [Pubmed]
  9. cDNA cloning of ovine pulmonary SP-A, SP-B, and SP-C: isolation of two different sequences for SP-B. Pietschmann, S.M., Pison, U. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  10. Surfactant protein A enhances the phagocytosis of C1q-coated particles by alveolar macrophages. Watford, W.T., Smithers, M.B., Frank, M.M., Wright, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  11. Surfactant protein A and lipid are internalized via the coated-pit pathway by type II pneumocytes. Stevens, P.A., Wissel, H., Zastrow, S., Sieger, D., Zimmer, K.P. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  12. Surfactant metabolism. Ikegami, M., Jobe, A.H. Semin. Perinatol. (1993) [Pubmed]
  13. Transcription factors NF-kappaB and C/EBPdelta and IL-1-induced expression of surfactant protein A in lung explants during the perinatal period. Seppänen, O., Glumoff, V., Paananen, R., Rounioja, S., Hallman, M. Biol. Neonate (2005) [Pubmed]
  14. Endocytosed SP-A and surfactant lipids are sorted to different organelles in rat type II pneumocytes. Wissel, H., Lehfeldt, A., Klein, P., Müller, T., Stevens, P.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  15. Enhanced surfactant protein and defensin mRNA levels and reduced viral replication during parainfluenza virus type 3 pneumonia in neonatal lambs. Grubor, B., Gallup, J.M., Meyerholz, D.K., Crouch, E.C., Evans, R.B., Brogden, K.A., Lehmkuhl, H.D., Ackermann, M.R. Clin. Diagn. Lab. Immunol. (2004) [Pubmed]
  16. Postnatal lung function in lambs after fetal hormone treatment. Effects of gestational age. Ikegami, M., Polk, D.H., Jobe, A.H., Newnham, J., Sly, P., Kohen, R., Kelly, R. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  17. Surfactant metabolism in surfactant protein A-deficient mice. Ikegami, M., Korfhagen, T.R., Bruno, M.D., Whitsett, J.A., Jobe, A.H. Am. J. Physiol. (1997) [Pubmed]
  18. Re-expression of pulmonary surfactant proteins following tracheal obstruction in fetal sheep. Lines, A., Gillett, A.M., Phillips, I.D., Wallace, M.J., Hooper, S.B. Exp. Physiol. (2001) [Pubmed]
  19. Surfactant phospholipids and proteins are increased in fetal sheep with pulmonary hypertension secondary to fetal systemic arteriovenous fistula. Benachi, A., Jouannic, J.M., Barlier-Mur, A.M., Chailley-Heu, B., Bourbon, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  20. Decreased surfactant proteins in lambs with pulmonary hypertension secondary to increased blood flow. Gutierrez, J.A., Parry, A.J., McMullan, D.M., Chapin, C.J., Fineman, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  21. Surfactant protein expression is increased in the ipsilateral but not contralateral lungs of fetal sheep with left-sided diaphragmatic hernia. Davey, M.G., Biard, J.M., Robinson, L., Tsai, J., Schwarz, U., Danzer, E., Adzick, N.S., Flake, A.W., Hedrick, H.L. Pediatr. Pulmonol. (2005) [Pubmed]
  22. Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis. Lesur, O., Veldhuizen, R.A., Whitsett, J.A., Hull, W.M., Possmayer, F., Cantin, A., Bégin, R. Lung (1993) [Pubmed]
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