Am. J. Respir. Cell Mol. Biol., Vol 15, No. 6, Dec 1996, 731-737.
Protection of human nasal respiratory epithelium from complement- mediated lysis by cell-membrane regulators of complement activation
S Varsano, I Frolkis, L Rashkovsky, D Ophir and Z Fishelson
Department of Pulmonary Medicine, Meir General Hospital, Tel-Aviv, Israel.
Complement in the respiratory tract protects the host from invading
micoorganisms and other inhaled insults, but may damage normal tissue.
Recently we reported that human respiratory epithelium from the nose to the
alveoli expresses three cell-membrane regulators of complement activation:
membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF;
CD55), and CD59. In this study we investigated whether two of these
complement-regulatory proteins, DAF and CD59, protect human nasal
epithelial cells from complement-mediated lysis. Treatment of nasal
epithelial cells in suspension with 50% or 100% normal human serum (NHS)
lysed small percentages of cells (8% and 16%, respectively). Addition of
complement activators, rabbit serum antinasal epithelial cells (anti-NEC),
or lipopolysaccharide (LPS) increased cell lysis in the presence of 50% NHS
in a dose-dependent manner up to 50% and 35% lysis, respectively. Human
serum deficient in C3 or C7 did not lyse nasal epithelial cells even in the
presence of anti-NEC. To assay the contribution of DAF and CD59 to cell
protection against lysis, nasal epithelial cells in suspension were treated
with appropriate blocking antibodies. Both anti-DAF and anti-CD59 markedly
increased the susceptibility of human nasal epithelial cells to lysis by
complement. At 50% NHS, anti-DAF and anti-CD59 antibodies increased
epithelial cell lysis from 8% to 24% and 67%, respectively. A similar
pattern of response to complement was demonstrated by monolayers of
substrate-anchored cultured cells. These results indicate that DAF and CD59
protect human nasal epithelial cells from complement-mediated lysis;
however, intense activation of complement may overcome this protection,
leading to cell death and tissue injury. We speculate that imbalance
between complement regulation and complement activation in the human
respiratory tract in disease may result in tissue injury and impaired
tissue function.
