the physiological role of individual leukocyte integrins studies using genetificient (knockout) mice  Page description

Help  Print 
Back »
 

Details of project

  
Identifier
46409
Type K
Principal investigator Mócsai, Attila
Title in Hungarian Az egyes fehérjesejt-integrinek élettani szerepének vizsgálata génhiányos (knockout) egerek segítségével
Title in English the physiological role of individual leukocyte integrins studies using genetificient (knockout) mice
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Dept. of Physiology (Semmelweis University)
Participants Fodor, Szabina
Hamar, Péter
Jakus, Zoltán
Káldi, Krisztina
Starting date 2004-01-01
Closing date 2008-12-31
Funding (in million HUF) 10.062
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
A támogatott kutatások során a neutrofil granulociták működését vizsgáltuk genetikai, biokémiai és farmakológiai megközelítésekkel. Legfontosabb tudományos eredményeink alábbiak voltak: 1) A neutrofil granulociták integrinjei önmagukban nem képesek a sejtek teljes aktiválódását létrehozni (Jakus et al., J Immunol 2004; IF: 6.70) 2) A humán genom a korábban feltételezettnél lényegesen több ITAM-tartalmú molekulát kódol (Fodor et al., Immunol Lett 2006; IF: 2.14) 3) Az integrinek jelátvitele ITAM-függő mechanizmusokon keresztül jön létre (Mócsai et al., Nat Immunol 2006; IF: 27.60) 4) Egy új integrin-jelátviteli modell felállítása (Jakus et al., Trends Cell Biol 2007;IF: 12.43) 5) Egér neutrofilek immunkomplex-mediált aktiválódása az FcgammaRIII és az FcgammaRIV együttműködésével jön létre (Jakus et al., J Immunol 2008; IF: 6.29) Ezek az eredmények nagyban járulnak hozzá a neutrofilek működésének és az autoimmun gyulladásos folyamatok patomechanizmusának megértéséhez.
Results in English
The sponsored research activity focused on the analysis of neutrophil functions by genetic, biochemical and pharmacological approaches. Our most important observations were the following: 1) Neutrophil integrins by themselves are not able to induce full activation of the cells (Jakus et al., J Immunol 2004; IF: 6.70) 2) The human genome contains significantly more ITAM-containing adapters than previousy thought (Fodor et al., Immunol Lett 2006; IF: 2.14) 3) Integrins utilize an ITAM-based signal transduction mechanism (Mócsai et al., Nat Immunol 2006; IF: 27.60) 4) Development of a new integrin signal transduction model (Jakus et al., Trends Cell Biol 2007;IF: 12.43) 5) Activation of murine neutrophils by immune complexes proceeds through a cooperative action of FcgammaRIII and FcgammaRIV (Jakus et al., J Immunol 2008; IF: 6.29) These results will strongly contribute to the understanding of neutrophil functions and the pathomechanism of autoimmune inflammatory diseases.
Full text http://real.mtak.hu/1421/
Decision
Yes





 

List of publications

  
Zoltán Jakus, Giorgio Berton, Erzsébet Ligeti, Clifford A. Lowell and Attila Mócsai: Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity Fcgamma-Receptors: Full Activation Requires both Integrin and ..., Magyar Immunológia 2004/3: 38-39., 2004
Zoltán Jakus, Erzsébet Ligeti, Clifford A. Lowell and Attila Mócsai: Cross-linking of integrins is not sufficient for full activation of neutrophils: Anti-integrin antibodies ..., European Journal of Clinical Investigation, 34 (Suppl 1): 49, 2004
Mócsai A, Humphrey MB, Van Ziffle JAG, Lanier LL, Nakamura MC and Lowell CA: An Immunoreceptor-Like Mechanism Is Required for Adhesion Receptor Signaling in Multiple Phagocytic Lineages, Clinical and Investigative Medicine Suppl, 27: 10B, 2004
Jakus Z, Németh T és Mócsai A: Az Fcgamma-receptor-jelátvitel vizsgálata neutrophil granulocytákban, Magyar Immunológia 2005/2. 21. o., 2005
Mócsai A, Humphrey MB, Lowell CA and Nakamura MC: Immunoreceptor-like signaling in osteoclasts, Eur J Clin Invest 2005, 35 (Suppl 2): 43., 2005
Jakus Z, Berton G, Ligeti E, Lowell CA and Mócsai A: Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low-Affinity Fc-receptors, J Leukoc Biol 2005, 51 (Suppl S): 34., 2005
Mócsai A: Intracellular signalling in neutrophils and osteoclasts, FEBS J 2005, 272 (Suppl 1): 4., 2005
Jakus Z, Németh T és Mócsai A: Fcgamma-receptor signaling in neutrophil granulocytes, Acta Physiol Hung 2005, 92: 265-266., 2005
Jakus Z, Abram CL, Lowell CA and Mócsai A: An immunoreceptor-like mechanism is required for integrin signaling in neutrophils, Eur J Clin Invest 2005, 35 (Suppl 2): 45., 2005
Jakus Z, Németh T and Mócsai A: Fcgamma-receptor signaling in neutrophils, Eur J Clin Invest 2006, 36 (Suppl 1): 31, 2006
Abram CL, Jakus Z, Kovács M, Lanier LL, Lowell CA and Mócsai A: An ITAM-based mechanism is required for integrin signaling of neutrophils, Eur J Clin Invest 2006, 36 (Suppl 1): 32, 2006
Walzog B, Schymeinsky J, Sindrilaru A, Gerstl R, Mócsai A and Scharfetter-Kochanek K: beta2 integrin (CD11/CD18)-mediated signaling via Syk and Vav is critical for neutrophil migration and phagocytosis, Eur J Clin Invest 2006, 36 (Suppl 1): 33, 2006
Kovács M, Kertész Z, Jakus Z, Settleman J and Mócsai A: Neutrophil function in the absence of the p190-B Rho GAP, Eur J Clin Invest 2006, 36 (Suppl 1): 82, 2006
Németh T, Jakus Z and Mócsai A: Phospholipase Cgamma2 is required for Fc-receptor and integrin signaling in neutrophils, Eur J Clin Invest 2006, 36 (Suppl 1): 82, 2006
Zoltán Jakus, Giorgio Berton, Erzsébet Ligeti, Clifford A. Lowell and Attila Mócsai: Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity Fcgamma-Receptors: Full Activation Requires both Integrin and ..., Journal of Immunology, 173: 2068-2077, 2004
Berton G, Mócsai A and Lowell CA: Src and Syk Kinases: Key Regulators of Phagocytic Cell Activation., Trends Immunol 2005, 26: 208-214, 2005
Fodor S, Jakus Z and Mócsai A: ITAM-based signaling beyond the adaptive immune response, Immunol Lett 2006, 104: 29-37, 2006
Mócsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA: Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs., Nat Immunol 2006, 7: 1326-1333, 2006
Schymeinsky J, Sindrilaru A, Frommhold D, Sperandio M, Gerstl R, Then C, Mócsai A, Scharffetter-Kochanek K, and Walzog B: The Vav binding site of the non–receptor tyrosine kinase Syk at Tyr 348 is critical for beta2 integrin (CD11/CD18)–mediated neutrophil migration, Blood 2006, 108: 3919-3927, 2006
Frommhold D, Mannigel I, Schymeinsky J, Mócsai A, Poeschl J, Walzog B and Sperandio M.: Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo, BMC Immunol 2007, 8:31, 2007
Jakus Z, Fodor S, Abram CL, Lowell CA and Mócsai A: Immunoreceptor-like signaling by beta2 and beta3 integrins, Trends Cell Biol 2007, 17: 493-501, 2007
Schymeinsky J, Mócsai A and Walzog B: Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications, Thromb Haemost 2007, 98: 262-273, 2007
Jakus Z, Németh T, Verbeek JS and Mócsai A: Critical but overlapping role of FcgammaRIII and FcgammaRIV in activation of murine neutrophils by immobilized immune complexes, J Immunol 2008, 180:618-629, 2008



Back »