Enhanced proliferation and decreased apoptosis in lung lavage cells of sarcoidosis patients.
BACKGROUND
Sarcoidosis is a systemic autoimmune disease where an inflammatory reaction involving alveolar macrophages, T-helper lymphocytes, and epitheloid cells is mounted against unknown antigens. A genetic predisposition for sarcoidosis is supposed by studies in twins, by geographical and racial distribution. In the current investigation we compared the expression patterns between slow onset and acute sarcodosis using a whole-genome cDNA array.


METHODS
Bronchoalveolar lavage was performed in six patients with slow onset sarcoidosis and four patients with acute sarcoidosis (Löfgren's disease) and obtained cells were used for gene expression profiling. The results were confirmed by RT- and Taqman-PCR. In addition, protein expression was examined on paraffin sections of sarcoid granulomas by immunohistochemistry.


RESULTS
In T-helper lymphocytes and alveolar macrophages we found an upregulation of genes belonging to the phosphoinositol-3-kinase/v-akt murine thymoma viral oncogene homolog/signal transducer and activator of transcription 3 pathway, as well as a downregulation of genes of the extrinsic and intrinsic apoptotic signaling cascades. In addition an upregulation of the genes encoding fatty acid binding protein 4 and 5, as well as peroxisome proliferative activated receptor delta in Löfgren's disease was detected. Differences in gene expression between slow onset sarcoidosis and Löfgren's syndrome were found mainly within genes of the major histocompatibility complex.


CONCLUSIONS
In sarcoidosis enhanced cell proliferation and decreased apoptosis result in accumulation and prolonged survival of antigen-primed T-helper lymphocytes and activated macrophages. This is enhanced in Löfgren's disease, probably by hyper-stimulation via the peroxisome proliferation signaling, providing a larger pool of antigen-primed immune cells.
Institute of Pathology, Laboratories for Molecular Cytogenetics, Environmental & Respiratory Pathology, Graz, Austria.
Susanna
S
Petzmann
Christian
C
Maercker
Eva
E
Markert
Izidor
I
Kern
Katharina
K
Osolnik
Wolfgang
W
Pohl
Helmut H
HH
Popper
D000208:Acute Disease; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008262:Macrophage Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D050796:STAT3 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt