title: Leukocyte integrin activation mediates transient neutropenia after G-CSF administration.
abstract: After administration of granulocyte colony-stimulating factor (G-CSF), there is a marked, albeit transient, drop in circulating neutrophils. To determine the role of leukocyte integrins in this disappearance, a dog having canine leukocyte adhesion deficiency (CLAD) or CLAD dogs who had undergone gene correction either by matched littermate allogeneic transplant or autologous gene therapy were evaluated. Shortly after G-CSF administration, a dramatic, yet transient, neutropenia was observed in the control littermates. This neutropenia was not as marked in the CLAD dogs. In all instances, it was CD18(+) neutrophils that preferentially egressed from the circulation. The association of CD18 with this rapid loss suggested leukocyte integrin activation after G-CSF administration. To determine the activation status of the integrin, a monoclonal antibody recognizing the activated α-subunit cation binding domain (mAb24) was used to evaluate human leukocytes after G-CSF administration. Mirroring the dramatic decrease in circulating neutrophil numbers, there was a dramatic and specific increase in the activation of the α-subunit after G-CSF expression on polymorphonuclear leukocytes. This activation, like the drop in neutrophil count, was transient. These results demonstrate that the leukocyte integrin on circulating neutrophils is transiently activated after G-CSF administration and mediates the transient neutropenia observed after G-CSF administration.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, Rockville, MD, USA. donahuer@nhlbi.nih.gov
authors.forename: Robert E
authors.initials: RE
authors.lastname: Donahue
authors.forename: Laura
authors.initials: L
authors.lastname: Tuschong
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bauer
authors.forename: Yu Ying
authors.initials: YY
authors.lastname: Yau
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D009503:Neutropenia / Q000097:blood* / Q000139:chemically induced* / Q000235:genetics; D018375:Neutrophil Activation / Q000187:drug effects* / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism*
chemical_list: D018821:CD18 Antigens; D016179:Granulocyte Colony-Stimulating Factor