GM-CSF expression by human lung microvascular endothelial cells: in vitro and in vivo findings.
Recently, many findings indicate that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the pathogenesis of acute and chronic lung diseases. In the present paper, the production of this cytokine in human pulmonary microvascular endothelial cells (HPMEC) is investigated. In an in vitro study, quiescent HPMEC did not express GM-CSF, either at the transcriptional or at the protein level. After activation for 4 h with tumor necrosis factor (TNF)-alpha (30/300 U/ml), lipopolysaccharide (LPS; 0.1/1 microg/ml), or interleukin (IL)-1 beta (100 U/ml), a significant release of GM-CSF was measured by enzyme-linked immunosorbent assay, with a time-dependent increase over 72 h. IL-8 (4, 16, or 64 ng/ml) or IL-1 beta at a concentration of 10 U/ml did not induce the release of GM-CSF. Human umbilical vein endothelial cells (HUVEC) and the angiosarcoma cell line HAEND served as reference cell lines. GM-CSF release in HPMEC was significantly (P < 0.025-0.05) less inducible by IL-1 beta than in HUVEC. A constitutive expression of GM-CSF by HAEND was observed. Additionally, GM-CSF expression in vivo by the lung microvasculature was confirmed by immunohistochemistry in lung tissue. To our knowledge, this is the first report of the ability of human pulmonary endothelial cells to synthesize and release GM-CSF. These results support the hypothesis that the lung microvasculature via the production of GM-CSF is a potential contributor to the cytokine network in lung diseases. This could be of particular importance in the pathogenesis of the acute respiratory distress syndrome in which endothelial dysfunction plays a central pathogenetic role.
Institute of Pathology, Johannes Gutenberg University, 55101 Mainz, Germany.
Jürgen
J
Burg
Vera
V
Krump-Konvalinkova
Fernando
F
Bittinger
Charles James
CJ
Kirkpatrick
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006394:Hemangiosarcoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008833:Microcirculation; D011652:Pulmonary Circulation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor