Dichotomous roles for externalized cardiolipin in extracellular signaling: promotion of phagocytosis and attenuation of innate immunity

Details

• Personal Author:
  Balasubramanian K ; Bayir H ; Dar HH ; Fadeel B ; Jiang JF ; Kagan VE ; Kapralova VI ; Klein-Seetharaman J ; Klöditz K ; Lee JS ; Maeda A ; Mallampalli RK ; Mohammadyani D ; Polimova A ; Ray P ; St Croix CM ; Tyurin VA ; Tyurina YY ; Watkins S ; Xiong Z
• Description:
  Among the distinct molecular signatures present in the mitochondrion is the tetra-acylated anionic phospholipid cardiolipin, a lipid also present in primordial, single-cell bacterial ancestors of mitochondria and multiple bacterial species today. Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy. Given the immunogenicity of mitochondrial and bacterial membranes that are released during sterile and pathogen-induced trauma, we hypothesized that cardiolipins might function as "eat me" signals for professional phagocytes. In experiments with macrophage cell lines and primary macrophages, we found that membranes with mitochondrial or bacterial cardiolipins on their surface were engulfed through phagocytosis, which depended on the scavenger receptor CD36. Distinct from this process, the copresentation of cardiolipin with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide dampened TLR4-stimulated production of cytokines. These data suggest that externalized, extracellular cardiolipins play a dual role in host-host and host-pathogen interactions by promoting phagocytosis and attenuating inflammatory immune responses. [Description provided by NIOSH]
• Subjects:
  Immune System Lipids Occupational Health Safety
• Keywords:
  Cell-function Cellular-function Immune-reaction Immunology Lipid-peroxidation
• ISSN:
  1937-9145
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  8
• Issue:
  395
• NIOSHTIC Number:
  nn:20047444
• Citation:
  Sci Signal 2015 Sep; 8(395):ra95
• Contact Point Address:
  Krishnakumar Balasubramanian, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA
• Email:
  kris.balasub@gmail.com
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Science Signaling
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2f56dca6348003913d60df439012fe3916c6db0832d5c88bf449a8f0ac81c6c2ad6d126cdf67e2e1ed84963b59cb3206790feae1d64795a85562240e3231a665
• Download URL:
  https://stacks.cdc.gov/view/cdc/202504/cdc_202504_DS1.pdf
• File Type:
  [PDF - 1.43 MB ]