Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.
Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.
Balajthy
Zoltán
Z
Department of Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center, H-4012 Debrecen, Nagyerdei krt. 98, Hungary. zoli@indi.biochem.dote.hu
Csomós
Krisztián
K
Vámosi
György
G
Szántó
Attila
A
Lanotte
Michel
M
Fésüs
László
L
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000276:immunology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D010587:Phagocytosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013481:Superoxides / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D008562:Membrane Glycoproteins; D013481:Superoxides; D004247:DNA; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C008542:monodansylcadaverine; D002103:Cadaverine