Programmed Cell Clearance: S-Nitrosylation of Aminophospholipid Translocase Regulates Macrophage Engulfment of Target Cells

Details

• Personal Author:
  Basova L ; Bayir H ; Cai P ; Fadeel B ; Kagan VE ; Konduru NV ; Potapovich AI ; Quinn P ; Shvedova AA ; Stoyanovsky D ; Tyurin VA ; Tyurina YY ; Xue D
• Description:
  Aminophospholipid translocase (APT) is responsible for the asymmetric distribution of phosphatidylserine (PS) across the plasma membrane, thus preventing PS externalization. The enzyme can be S-nitrosylated resulting in the loss of its activity. We hypothesized that nitrosative stress - acting through APT S-nitrosylation - enhances PS externalization in cells by inhibiting APT activity. This pathway should be particularly important during inflammation whereby the oxidative/nitrosative burst generated by macrophages may cause direct nitrosylation or trans-nitrosylation of APT in target cells. To experimentally address this hypothesis we utilized H-60 cells that express high APT activity. S-nitroso-L-cysteine-ethyl ester (SNCEE) and S-nitroso-glutathione (GSNO) were used as prototypical cell-permeable and cell-impermeable trans-nitrosylating reagents. HL-60 cells externalized PS in response to SNCEE or GSNO treatment as evidenced by annexin V binding assay and fluorescence microscopy. No cytotoxic effects were induced by either of the trans-nitrosating agents. RAW 264.7 macrophages elicited enhanced phagocytosis towards "nitrosylated" HL-60 cells. Assessments of APT activity confirmed that S-nitrosylation is associated with an altered activity of the enzyme. We thus speculate that macrophage-induced nitrosative stress contributes to effective clearance of apoptotic cells and the regulation of inflammatory responses. [Description provided by NIOSH]
• Subjects:
  Amino Acids Cells, Cultured Cytotoxins Enzymes Occupational Health Safety
• Keywords:
  Amino-compounds Cell-cultures Cell-wall-permeability Cytotoxic-effects Cytotoxicity Microscopy Phagocytes
• Publisher:
  Human Frontier Science Program
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• NIOSHTIC Number:
  nn:20031103
• Citation:
  Sixth Human Frontier Science Program Awardees Annual Meeting, July 3-5, 2006, Paris, France. Strasbourg, Cedex, France: Human Frontier Science Program, 2006 Jul; :119
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Source Full Name:
  Sixth Human Frontier Science Program Awardees Annual Meeting, July 3-5, 2006, Paris, France
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1df517efb6332a8c7b43499876295cf82d17b9d3eff53f6b2950f2555628ee9c8a1c4c45fc9980849cffc2116e4db5b4d9fcd44c27bd216981f2a275fd9b516b
• Download URL:
  https://stacks.cdc.gov/view/cdc/191458/cdc_191458_DS1.pdf
• File Type:
  [PDF - 317.92 KB ]