- Open Access
On the significance of Surfactant Protein-A within the human lungs
© Goldmann et al; licensee BioMed Central Ltd. 2009
- Received: 06 March 2009
- Accepted: 12 March 2009
- Published: 12 March 2009
Surfactant Protein-A (SP-A) is the most prominent among four proteins in the pulmonary surfactant-system. SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC).
The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense.
By the use of cell culture or animal models the functional properties have been repeatedly shown in many aspects, often bearing surprising properties which strongly indicate the physiological importance of SP-A. To date SP-A is recognized as a molecule essential for pulmonary development, structure and function. An upcoming number of reports deals with the role of SP-A for pulmonary pathology. This article gives an overview about the state of knowledge on SP-A focused in applications for human pulmonary disorders and points out the importance for pathology-orientated research approaches using immunohistochemistry or in situ hybridization as promising methods to further elucidate the role of this molecule in adult lung diseases.
- Idiopathic Pulmonary Fibrosis
- Adult Respiratory Distress Syndrome
- Small Cell Lung Cancer Patient
- Pulmonary Pathology
- Adult Respiratory Distress Syndrome Patient
The role of the surfactant system for the development of the human lung is known to be essential. Since it is synthesized by humans starting in the 28th week of pregnancy and reaching functional levels in the 34th week, surfactant-substitution-therapy is a fundamental part of the treatment of premature babies suffering from Infant Respiratory Distress Syndrome (IRDS).
Pulmonary surfactant regulates dynamically the alveolar surface tension. The central role of the surfactant system for maintaining pulmonary function has been repeatedly shown by the use of cell culture or animal models .
Surfactant is a complex mixture of lipids, carbohydrates and four proteins (SP-A, SP-B, SP-C, SP-D). The initial descriptions of surfactant lead back to the 1950s, but little attention was given to the surfactant proteins until the 1980s . The genes coding for these proteins are located on different chromosomes. SP-B and SP-C are similarly structured hydrophobic proteins participating in the adsorption of phospholipids at the alveolar border, which leads to rapid reduction of the surface tension. The hydrophilic proteins SP-A and SP-D are members of the collectins with C-type lectin domains. SP-D together with SP-A play a role in the pulmonary defense against Gram-negative bacteria .
SP-A: biochemical properties and genetic organization
SP-A in pulmonary diseases
In recent years the role of defects in the expression of SP-A in context with different pulmonary diseases has become an issue of scientific investigations. Initially numerous studies have been performed to elucidate the role of surfactant substitution in pediatrics .
As one major function SP-A displays a protective role of the molecule in pulmonary host defense by interacting with various infectious agents such as bacteria, fungi and viruses. SP-A deficient knock-out mice – compared to wild type animals – are susceptible to infections with Pseudomonas aeruginosa  and the clearance of group B streptococcus is slower . In accordance the defense of SP-A deficient mice against Respiratory Syncytial Virus (RSV) has been shown to be reduced and may be restored by exogenous SP-A administration [15–17].
By mediating the attachment of Mycobacterium tuberculosis to alveolar macrophages and promoting the phagocytosis of these bacteria, SP-A is important in the pathogenesis of tuberculosis [18–21]. SP-A also functionally interacts with staphylococci [22, 23], Haemophilus influenza Type A [24, 25], Pneumocystis carinii [26, 27], Influenza A Virus (less efficient than SP-D) , Candida tropicalis  and Aspergillus fumigatus .
Therefore it is likely that defects in the expression of SP-A may be important in the course of non infectious pulmonary diseases of adult patients. In the case of idiopathic pulmonary fibrosis, for example, low levels of SP-A (measured by ELISA) have been reported in broncho alveolar lavages (BAL), but elevated levels were found in the sera [32–34]. Immunohistochemical examinations of the expression of SP-A in pulmonary fibrosis demonstrated evident defects by using specimens from different diseases displaying fibrotic changes in the lungs. In good agreement with the results in BAL reduced levels of SP-A have been observed in fibrotic lungs. This reduced SP-A-expression in fibrotic lungs may be caused by two reasons: a limited number of the SP-A producing type II pneumocytes and by a clearly reduced SP-A expression of the remaining cells .
Reduced levels of SP-A have been demonstrated also in other pulmonary diseases such as the Adult Respiratory Distress Syndrome (ARDS) and in pneumonia .
Keeping in mind that surfactant substitutes are widely available due to their application in pediatrics, a growing number of therapeutic possibilities may result from these findings.
Since SP-A represents a central molecule in pulmonary immunoregulation as well as in host-defense it is obvious that defects in the surfactant system may have functional influence in the course of these pulmonary disorders.
However, the choice of a suitable SP-A antibody is highly important since approaches using polyclonals display cross reactions with other tumors . This procedure has already become a part of pathological routine diagnosis, and – along with other markers such as the Thyroid-transcription-factor-1 (TTF-1) – the detection of SP-A (by PE-10) is a useful part of the immunohistochemical panel in pulmonary pathology.
Immunohistochemical detection of SP-A even might be utilized for forensic purposes helping to distinguish between fatal drowning and postmortem immersion .
Taken together, SP-A is a complexly regulated molecule with surprising properties and essential importance for pulmonary development, structure and function which is getting more and more into focus concerning various diseases of the adult lung. Thus, as an outlook, it will become an issue of pulmonary pathology which might provide promising perspectives for applications in research, diagnosis and therapy.
The authors thank J. Tiebach and M. Lammers for excellent technical assistance.
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