PROTECTION OF HUMAN NASAL RESPIRATORY EPITHELIUM FROM COMPLEMENT-MEDIATED LYSIS BY CELL-MEMBRANE REGULATORS OF COMPLEMENT ACTIVATION

Complement in the respiratory tract protects the host from invading mi coorganisms and other inhaled insults, but may damage normal tissue. R ecently we reported that human respiratory epithelium from the nose to the alveoli expresses three cell-membrane regulators of complement ac tivation: membrane cofactor protein (MCP, CD46), decay accelerating fa ctor (DAF; CD55), and CD59. In this study we investigated whether two of these complement-regulatory proteins, DAF and CD59, protect human n asal epithelial cells from complement-mediated lysis. Treatment of nas al epithelial cells in suspension with 50% or 100% normal human serum (NHS) lysed small percentages of cells (8 % and 16 %, respectively). A ddition of complement activators, rabbit serum antinasal epithelial ce lls (anti-NEC), or lipopolysaccharide (LPS) increased cell lysis in th e presence of 50% NHS in a dose-dependent manner up to 50% and 35 % ly sis, respectively. Human serum deficient in C3 or C7 did not lyse nasa l epithelial cells even in the presence of anti-NEC. To assay the cont ribution of DAF and CD59 to cell protection against lysis, nasal epith elial cells in suspension were treated with appropriate blocking antib odies. Both anti-DAF and anti-CD59 markedly increased the susceptibili ty of human nasal epithelial cells to lysis by complement. At 50% NHS, anti-DAF and anti-CD59 antibodies increased epithelial cell lysis fro m 8% to 24% and 67%, respectively. A similar pattern of response to co mplement was demonstrated by monolayers of substrate-anchored cultured cells. These results indicate that DAF and CD59 protect human nasal e pithelial cells from complement-mediated Iysis; however, intense activ ation of complement may overcome this protection, leading to cell deat h and tissue injury. We speculate that imbalance between complement re gulation and complement activation in the human respiratory tract in d isease may result in tissue injury and impaired tissue function.