Granulocyte colony-stimulating factor induces neutrophil sequestration in rabbit lungs.
The effects of intravenous injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on circulating neutrophil numbers, pulmonary vascular permeability, and morphologic changes in the lung were examined in rabbits. Intravenous injection of rhG-CSF caused a rapid, profound neutropenia due to neutrophil sequestration primarily within capillaries but also in larger microvessels of the lungs. Examination of neutrophil deformability using microfilters revealed that granulocyte colony-stimulating factor (G-CSF) treatment caused a rapid stiffening of neutrophils through the polymerization of F-actin but not microtubule assembly. The expression of CD11b, CD11c, and CD18 on human neutrophils after G-CSF treatment increased, but CD11a did not. Intravenous injection of rhG-CSF did not induce neutrophil emigration or albumin leakage into alveolar space, wet/dry lung weight ratios were unchanged, and no pathologic changes in lung histology were observed. These studies indicate that injection of rhG-CSF caused a rapid neutropenia and neutrophil sequestration in the lungs that is likely to be mediated through a G-CSF-induced decrease in neutrophil deformability, although neutrophil-endothelial cell adhesion may also play a role. However, this G-CSF-induced neutrophil sequestration did not induce a massive lung injury.
Inano
H
H
First Department of Medicine, Tokyo Women's Medical College, Tokyo, Japan.
Kameyama
S
S
Yasui
S
S
Nagai
A
A
D000818:Animals; D018845:CD11 Antigens / Q000032:analysis; D018821:CD18 Antigens / Q000032:analysis; D002196:Capillaries / Q000502:physiology; D002199:Capillary Permeability; D003599:Cytoskeleton / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D008168:Lung / Q000033:anatomy & histology / Q000098:blood supply*; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D011817:Rabbits; D011994:Recombinant Proteins
D018845:CD11 Antigens; D018821:CD18 Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor