WAVE1 mediates suppression of phagocytosis by phospholipid-derived DAMPs. 2013

Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
Research Center for Molecular Medicine of Austrian Academy of Sciences, Vienna, Austria.

Clearance of invading pathogens is essential to preventing overwhelming inflammation and sepsis that are symptomatic of bacterial peritonitis. Macrophages participate in this innate immune response by engulfing and digesting pathogens, a process called phagocytosis. Oxidized phospholipids (OxPL) are danger-associated molecular patterns (DAMPs) generated in response to infection that can prevent the phagocytic clearance of bacteria. We investigated the mechanism underlying OxPL action in macrophages. Exposure to OxPL induced alterations in actin polymerization, resulting in spreading of peritoneal macrophages and diminished uptake of E. coli. Pharmacological and cell-based studies showed that an anchored pool of PKA mediates the effects of OxPL. Gene silencing approaches identified the A-kinase anchoring protein (AKAP) WAVE1 as an effector of OxPL action in vitro. Chimeric Wave1(-/-) mice survived significantly longer after infection with E. coli and OxPL treatment in vivo. Moreover, we found that endogenously generated OxPL in human peritoneal dialysis fluid from end-stage renal failure patients inhibited phagocytosis via WAVE1. Collectively, these data uncover an unanticipated role for WAVE1 as a critical modulator of the innate immune response to severe bacterial infections.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D010530 Peritoneal Dialysis Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. Dialyses, Peritoneal,Dialysis, Peritoneal,Peritoneal Dialyses
D010538 Peritonitis INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs. Primary Peritonitis,Secondary Peritonitis,Peritonitis, Primary,Peritonitis, Secondary
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid

Related Publications

Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
January 1999, The international journal of biochemistry & cell biology,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
April 1981, Proceedings of the National Academy of Sciences of the United States of America,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
September 2014, Addiction biology,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
January 2016, Frontiers in bioscience (Scholar edition),
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
December 1965, Arthritis and rheumatism,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
February 2019, Cell death & disease,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
September 1992, Pharmaceutical research,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
April 2009, The Journal of surgical research,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
October 1968, The Journal of clinical investigation,
Ulrich Matt, and Omar Sharif, and Rui Martins, and Tanja Furtner, and Lorene Langeberg, and Riem Gawish, and Immanuel Elbau, and Ana Zivkovic, and Karin Lakovits, and Olga Oskolkova, and Bianca Doninger, and Andreas Vychytil, and Thomas Perkmann, and Gernot Schabbauer, and Christoph J Binder, and Valery N Bochkov, and John D Scott, and Sylvia Knapp
February 1988, Biochimica et biophysica acta,
Copied contents to your clipboard!