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Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06 Podcast
Human SP-A- genes, structure, function- and lung diseases

Human SP-A- genes, structure, function- and lung diseases

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06 vor 14 Jahren

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Surfactant associated protein-A (SP-A) is the most abundant
pulmonary surfactant protein and belongs to the family of innate
host defence proteins termed collectins. The aim of the study was
to elucidate the role of SP-A in human lung disease. This study was
designed to analyze the relation between genetics, structure and
function of SP-A in a CF, chronic bronchitis and asthma and healthy
control population ex vivo. Beginning with the analysis of SP-A
oligomeric forms, there were no correlations between serum and BAL
SP-A distribution forms. The forms showed only a significantly
different distribution comparing serum samples from bronchitis
patients and controls. In serum and BAL of CF patients the forms
containing the first peak were correlated with a better lung
function (Fev1 (% pred.)age20). Also higher relative SP-A amount in
the first peak is associated with a milder lung disease and a
better course of lung disease. Additionally, SP-A
self-agglutination is dependent on the amount of particular SP-A
oligomers present in a sample, i.e. the relative strength of SP-A
molecular forms in a sample. All SP-A structures self-agglutinate
in serum better than in BAL in samples of the patients groups while
in control samples BAL and serum SP-A showed the same abilities.
There was also a difference between the self-agglutination ability
of BAL samples from CF, Bro and control derived SP-A, but none in
serum. SP-A from control BAL agglutinated better than from
bronchitis BAL and this better than from CF BAL. These results are
also supported by the fact that a better agglutination ability of
SP-A was significantly associated with lung function. Therefore the
degree of the presence of active oligomeric forms within a BAL or
serum sample seems to be important for a better lung function
outcome. The SP-A oligomerization is associated with one SFTPA1
rs1136451 and one SFTPA2 SNP rs17881665 which are coupled, while
the mutated allele seems to cause a lack of complex oligomers. The
wildtype alleles of the SP-A2 SNPs rs1965708 and rs1975006 were
associated with CF compared to the bronchitis and control group.
There was a significant association between the mean ∆ Fev1
(%pred.) / year and V50L a SNP in the SFTPA1 gene (p = 0.0038)
while the mutated allele was associated with a worse course of lung
disease. The SP-A BAL level was significantly associated with the
SP-A1 SNP rs1136451 (p = 0.002) and the SP-A2 SNP rs17881665r (p =
0.002). The SP-A serum level was significantly associated with
SP-A1 N9T (p = 0.028). In addition in the CF study population there
was a significant association between the SP-A level in BAL and the
Fev1 (% pred.) estimated for age 20 (p = 0.009). The higher the
SP-A levels were in BAL the bigger were the values of the Fev1 (%
pred.) estimated for age 20. There was no correlation between the
SP-A BAL or serum level and any other clinical characteristic such
as BMI, age, gender, IgG or IgE in serum. In conclusion, these
results indicate a very important role for SP-A in human lung
immunity. Future areas for clinical research include disease
specific SP-A expression pattern and their functional consequences,
the differential roles of SP-A1 and SP-A2 in human lung diseases,
and therapeutic approaches to correct altered SP-A levels.