Protection of human nasal respiratory epithelium from complement-mediated lysis by cell-membrane regulators of complement activation
| Autor: | Dov Ophir, Zvi Fishelson, Shabtai Varsano, Ludmila Rashkovsky, Inna Frolkis |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Cytotoxicity Immunologic Pulmonary and Respiratory Medicine Adolescent Clinical Biochemistry CD59 Antigens chemical and pharmacologic phenomena Mucous membrane of nose CD59 Biology Epithelium Membrane Cofactor Protein Complement Inactivator Proteins Antigens CD medicine Humans Child Molecular Biology Decay-accelerating factor Cells Cultured Membrane Glycoproteins CD55 Antigens CD46 Complement System Proteins Cell Biology Middle Aged Molecular biology Complement system Nasal Mucosa medicine.anatomical_structure Immunology Respiratory epithelium |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 15:731-737 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.15.6.8969267 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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