TY - JOUR
T1 - Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line
AU - Varsano, Shabtai
AU - Kaminsky, Marina
AU - Kaiser, Meirav
AU - Rashkovsky, Ludmila
PY - 2000
Y1 - 2000
N2 - Background - The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells. Methods - Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis. Results - Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/106 cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1α (100 U/ml/72 h) and tumour necrosis factor (TNF-α; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-γ (10 U/ml/72 h) and TNF-α (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1α, TNF-α, or IFN-γ. Conclusions - Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.
AB - Background - The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells. Methods - Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis. Results - Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/106 cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1α (100 U/ml/72 h) and tumour necrosis factor (TNF-α; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-γ (10 U/ml/72 h) and TNF-α (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1α, TNF-α, or IFN-γ. Conclusions - Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.
KW - Bronchial epithelium
KW - Complement inhibitory proteins
KW - Complement proteins
KW - Cytokines
UR - http://www.scopus.com/inward/record.url?scp=0034054892&partnerID=8YFLogxK
U2 - 10.1136/thorax.55.5.364
DO - 10.1136/thorax.55.5.364
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C2 - 10770816
AN - SCOPUS:0034054892
SN - 0040-6376
VL - 55
SP - 364
EP - 369
JO - Thorax
JF - Thorax
IS - 5
ER -