PMID: 9636192Jun 24, 1998Paper

Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr

Proceedings of the National Academy of Sciences of the United States of America
C A Lowell, G Berton

Abstract

Signal transduction through the leukocyte integrins is required for the processes of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory reactions. Neutrophils isolated from knockout mice that are deficient in the expression of p59/61(hck) (Hck) and p58(c-fgr) (Fgr), members of the Src-family of protein tyrosine kinases, have been shown to be defective in adhesion mediated activation. Cells from these animals have impaired induction of respiratory burst and granule secretion following plating on surfaces that crosslink beta2 and beta3 integrins. To determine if the defective function of hck-/-fgr-/- neutrophils observed in vitro also results in impaired inflammatory responses in vivo, we examined responses induced by lipopolysaccharide (LPS) injection in these animals. The hck-/-fgr-/- mice showed marked resistance to the lethal effects of high-dose LPS injection despite the fact that high levels of serum tumor necrosis factor alpha and interleukin 1alpha were detected. Serum chemistry analysis revealed a marked reduction in liver and renal damage in mutant mice treated with LPS, whereas blood counts showed a marked neutrophilia that was not seen in wild-type animals. Direct examination of liver section...Continue Reading

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Citations

Mar 31, 2005·Trends in Immunology·Giorgio BertonClifford A Lowell
Mar 26, 2002·Critical Care Clinics·Rachel G Khadaroo, John C Marshall
Oct 26, 1999·Cellular Signalling·G Berton, C A Lowell
Oct 16, 2002·The International Journal of Biochemistry & Cell Biology·Derek StrassheimEdward Abraham
Feb 9, 2000·The Journal of Experimental Medicine·H D GreshamC L Willman
May 3, 2000·Journal of Hematotherapy & Stem Cell Research·S Sinha, S J Corey
May 25, 2001·Critical Care Medicine·F Garcia SorianoC Szabó
Jan 23, 1999·Current Opinion in Hematology·G Berton
Jul 19, 2000·Infection and Immunity·C Astarie-DequekerI Maridonneau-Parini
Dec 2, 2004·Molecular and Cellular Biology·Regina A ClemensErik J Peterson
Feb 24, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Yongquan ShiKatherine A Siminovitch
Oct 31, 2008·American Journal of Physiology. Renal Physiology·Renee E YuraJudith S Bond
Jan 25, 2005·American Journal of Respiratory and Critical Care Medicine·Mariano SevergniniAmy R Simon
Nov 6, 2001·American Journal of Respiratory Cell and Molecular Biology·J H LeeD Sheppard
Jun 10, 2008·American Journal of Respiratory Cell and Molecular Biology·Slava EpelmanChristopher H Mody
Jul 3, 2004·The Journal of Clinical Investigation·Wen-Hai ChouRobert O Messing
Nov 1, 2006·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Daisuke Okutani
Oct 22, 2014·Cellular and Molecular Life Sciences : CMLS·Agnieszka PłóciennikowskaKatarzyna Kwiatkowska
Jan 1, 2008·Expert Opinion on Medical Diagnostics·Laurie L Parker, Stephen J Kron
Jan 19, 2016·Immunity·Stephanie VolmeringAlexander Zarbock
Sep 20, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Stig Bengmark
Sep 30, 2009·Experimental Hematology·Cara K FraserJohn D Hayball
Aug 25, 2006·Anesthesiology Clinics·Stig Bengmark
Jul 7, 2005·Traffic·Céline CougouleIsabelle Maridonneau-Parini
Nov 17, 2009·Immunological Reviews·Jinyi ZhangKatherine A Siminovitch
Nov 25, 2004·Experimental Cell Research·Silvia ContinoloGiorgio Berton

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