Granulocyte macrophage colony stimulating factor induced changes in cellular adhesion molecule expression and adhesion to endothelium: in-vitro and in-vivo studies in man.
The administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) causes a transient leucopenia. Radionuclide labelling studies showed this to be due to margination of neutrophils and monocytes predominantly in the pulmonary vasculature. No evidence of complement activation was found. A rapid in-vivo rise in neutrophil cellular adhesion molecule (CAM) expression was observed paralleling the development of the neutropenia. Neutrophils exposed to rhGM-CSF in-vitro showed similar rapid increases in CAM expression. The adherence of chromium-labelled neutrophils to endothelial cell cultures was modestly but highly significantly increased by rhGM-CSF, an effect that was reduced by the binding of a monoclonal antibody to the beta chain of neutrophil CAM. The margination of phagocytic cells induced by rhGM-CSF administration is therefore likely to be due at least in part to increased expression of adhesion promoting glycoproteins. The demargination, however, occurred at a time when neutrophil CAM expression was still high, suggesting that dissociation of the neutrophil-endothelial cell interaction depends on factors other than downregulation of CAM expression. In-vivo modulation of phagocyte CAMS and adhesive properties by GM-CSF may be of importance in the normal inflammatory response.
Devereux
S
S
Department of Haematology, University College and Middlesex Hospital School of Medicine, London.
Bull
H A
HA
Campos-Costa
D
D
Saib
R
R
Linch
D C
DC
D000954:Antigens, Surface / Q000032:analysis*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D003115:Colony-Stimulating Factors / Q000009:adverse effects*; D004727:Endothelium / Q000503:physiopathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000009:adverse effects*; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000209:etiology* / Q000503:physiopathology; D009000:Monocytes / Q000502:physiology; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils / Q000502:physiology
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor