title: Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia.
abstract: Severe congenital neutropenia (SCN) or Kostmann syndrome is a disorder of myelopoiesis characterized by a maturation arrest at the stage of promyelocytes or myelocytes in bone marrow and absolute neutrophil counts less than 200/microL in peripheral blood. Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients. To date, little is known regarding the underlying pathomechanism of SCN. G-CSF-induced neutrophils of patients with SCN are functionally defective (eg, chemotaxis, superoxide anion generation, Ca(++ )mobilization). Two guanosine triphosphatases (GTPases), Rac2 and RhoA, were described to be involved in many neutrophil functions. The expression of these GTPases and their regulation in patients' neutrophils were of interest. This study determined that the guanosine diphosphate (GDP)-dissociation inhibitor RhoGDI is overexpressed at the protein level in patients' neutrophils and that overexpression is a result of G-CSF treatment. RhoA and LyGDI are expressed at similar levels, whereas Rac2 shows a decreased expression. In addition, association of Rac2 and RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression in patients' neutrophils. (Blood. 2000;95:2947-2953)
authors.affiliation: Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany. bkasper@fz-borstel.de
authors.forename: B
authors.initials: B
authors.lastname: Kasper
authors.forename: N
authors.initials: N
authors.lastname: Tidow
authors.forename: D
authors.initials: D
authors.lastname: Grothues
authors.forename: K
authors.initials: K
authors.lastname: Welte
mesh_terms: D020730:Guanine Nucleotide Dissociation Inhibitors / Q000097:blood / Q000235:genetics*; D006801:Humans; D009503:Neutropenia / Q000097:blood* / Q000151:congenital / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism*; D019000:Phosphotyrosine / Q000097:blood; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D020744:rac GTP-Binding Proteins / Q000097:blood / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000097:blood / Q000235:genetics; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020742:rhoA GTP-Binding Protein / Q000097:blood / Q000235:genetics*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D019000:Phosphotyrosine; D011506:Proteins; D025521:Tumor Suppressor Proteins; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020742:rhoA GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C569638:ARHGDIA protein, human; C569658:ARHGDIB protein, human