Abnormal regulation in the signal transduction in neutrophils from patients with severe congenital neutropenia - relation of impaired mobilization of cytosolic free calcium to altered chemotaxis, superoxide anion generation and F-actin content

Severe congenital neutropenia (SCN) can be corrected in vivo by treatment with pharmacological dosages of recombinant human granulocyte colony-stimulating factor (rhg-CSF). In order to analyze the decreased chemotaxis of neutrophils from SCN patients receiving rhg-CSF, neutrophil functions essential for chemotaxis were investigated. The mobilization of cytosolic calcium (Ca2+)i and the functional state of cytoskeletal proteins in neutrophils from SCN patients were compared with either neutrophils from healthy donors and neutrophils from patients with chemotherapy-induced neutropenia also receiving rhg-CSF. Using flow cytometric analysis, two neutrophil subpopulations were detected in SCN patients in response to N-formylmethionine leucyl-phenylalanine (FMLP) (10(-9) M to 10(-7) M), one of which was unable to respond to this stimulus with an increase in (Ca2+)i.