Author/Editor		Petzmann, Susanna; Maercker, Christian; Markert, Eva; Kern, Izidor; Osolnik, Katharina; Pohl, Wolfgang; Popper, Helmut H
Title		Enhanced proliferation and decreased apoptosis in lung lavage cells of sarcoidosis patients
Type		članek
Source		Sarcoidosis Vasc Diffuse Lung Dis
Vol. and No.		Letnik 23
Publication year		2006
Volume		str. 190-200
Language		eng
Abstract		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 (Lofgren's disease) and obtained cells were used for gene expression profiling. The results were confirmed by RT and Taqman-PE. 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 Lofgren's disease was detected. Differences in gene expression between slow onset sarcoidosis and Lofgren's syndrome were found mainly within genes of the major histocompatibility complex. Conclusions: In sarcoidosis enhanced cell profiferation and decreased apoptosis result in accumulation and prolonged survival of antigen-primed T helper lymphocytes and activated macrophages. This is enhanced in Lofgren's disease, probably by hyper-stimulation via the peroxisome proliferation signaling, providing a larger pool of antigen-primed immune cells.
Descriptors		SARCOIDOSIS, PULMONARY BRONCHOALVEOLAR LAVAGE APOPTOSIS CELL DIVISION T-LYMPHOCYTES, HELPER-INDUCER POLYMERASE CHAIN REACTION IMMUNOHISTOCHEMISTRY GENE EXPRESSION MACROPHAGES, ALVEOLAR SEQUENCE ANALYSIS, DNA