PI3Kβ plays a critical role in neutrophil activation by immune complexes

Science Signaling

Volumn 4, Issue 168, 2011, Pages

  Kulkarni, Suhasini ^a   Sitaru, Cassian ^b,c   Jakus, Zoltan ^d   Anderson, Karen E ^a   Damoulakis, George ^a   Davidson, Keith ^a   Hirose, Misa ^b   Juss, Jatinder ^a   Oxley, David ^a   Chessa, Tamara A M ^a   Ramadani, Faruk ^a   Guillou, Herve ^a   Segonds Pichon, Anne ^a   Fritsch, Anja ^e   Jarvis, Gavin E ^f   Okkenhaug, Klaus ^a   Ludwig, Ralf ^b   Zillikens, Detlef ^b   Mocsai, Attila ^d   Vanhaesebroeck, Bart ^g   Stephens, Len R ^a   Hawkins, Phillip T ^a   more..

^a BABRAHAM INSTITUTE   (United Kingdom)

^b UNIVERSITY OF LÜBECK   (Germany)

^c UNIVERSITY OF FREIBURG   (Germany)

^d SEMMELWEIS UNIVERSITY OF MEDICINE   (Hungary)

^e UNIVERSITY OF FREIBURG   (Germany)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; AUTOANTIBODY; FC RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; IMMUNOGLOBULIN G; LEUKOTRIENE B4; LEUKOTRIENE B4 RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE BETA; PHOSPHATIDYLINOSITOL 3 KINASE DELTA; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; CD2 ANTIGEN; ENZYME INHIBITOR; IMMUNOGLOBULIN HEAVY CHAIN; LTB4R1 PROTEIN, MOUSE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN ANTIBODY COMPLEX; ARTICLE; AUTOIMMUNE DISEASE; BLISTER; CONTROLLED STUDY; ENZYME DEFICIENCY; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; KNOCKOUT MOUSE; LEUKOCYTE ACTIVATION; MOUSE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; ANIMAL; B LYMPHOCYTE; DRUG ANTAGONISM; DRUG EFFECT; FEMALE; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENE REARRANGEMENT; GENETICS; IMMUNOGLOBULIN STRUCTURE; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOLOGY; MALE; METABOLISM; MOUSE MUTANT; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; WESTERN BLOTTING;

MUS;

ANIMALS; ANTIGEN-ANTIBODY COMPLEX; ANTIGENS, CD2; B-LYMPHOCYTES; BLOTTING, WESTERN; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; ENZYME INHIBITORS; FEMALE; FLOW CYTOMETRY; GENE REARRANGEMENT, B-LYMPHOCYTE; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN JOINING REGION; IMMUNOGLOBULIN VARIABLE REGION; IN SITU HYBRIDIZATION, FLUORESCENCE; MALE; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NEUTROPHIL ACTIVATION; NEUTROPHILS; REACTIVE OXYGEN SPECIES; RECEPTORS, IGG; RECEPTORS, LEUKOTRIENE B4; SIGNAL TRANSDUCTION;

EID: 79954517766     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001617     Document Type: Article

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60. Acknowledgments: We thank members of the Small Animal Breeding Unit at the Babraham Institute for animal husbandry and J. Webster for help with mass spectrometry experiments. We also thank K. Boyle, H. Welch, S. Vermeren, F. Colucci, and M. Turner for critical review of the manuscript, and J. Swanson, M. Peters-Golden, and L. Gambardella for helpful discussions. Funding: This study was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/DO13593/1 and BBS/B/ 01979), British Lung Foundation, Wellcome Trust (WT085889MA), and the CJ Martin Fellowship awarded to S.K. by the National Heart Foundation (Australia) and the National Health and Medical Research Council (Australia), and funding awarded to C.S. and D.Z. by the Dr. Robert Pfleger-Stiftung (15.11.06) and Excellence Initiative of the German Federal and State Governments (EXC 294). Z.J. and A.M. were funded by the European Research Council (Starting Independent Investigator grant 206283). Z.J. was also funded by a Bolyai Research Fellowship from the Hungarian Academy of Sciences. R.L. and M.H. were funded by DFG EXC 306/1 and DFG LU 877/5-1. The gene-targeted mice used in this study were funded by the Ludwig Institute for Cancer Research, USA. Author contributions: S.K. designed, performed, and analyzed the experiments and helped to prepare the manuscript; C.S. designed and performed the EBA experiments; Z.J. designed, performed, and analyzed all of the K/BxN experiments; K.E.A., G.D., K.D., M.H., D.O., J.J., T.A.M.C., F.R., and H.G. performed the experiments; A.F. generated hcVII; G.E.J. provided FcR γ chain knockout mice; A.S.-P. performed statistical analysis; K.O. supervised and designed the lymphocyte experiments; R.L. and D.Z. supervised and designed the EBA experiments; A.M. supervised and designed the K/BxN experiments; B.V. supervised and designed the generation of PI3Kβ transgenic mice; L.R.S. and P.T.H. were responsible for overall supervision of the project, designed the experiments, and prepared the manuscript. Competing interests: Use of the p110β and p110δ mice requires a material transfer agreement (MTA) from the Ludwig Institute for Cancer Research. Use of the KRN transgenic mice requires an MTA from Semmelweis University and IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), France. B.V. is a consultant and Science Advisory Board member of Intellikine, San Diego, CA. K.O. is a paid consultant for GlaxoSmithKline.