Granulocyte colony‐stimulating factor down‐regulates the surface expression of the human leucocyte adhesion molecule‐1 on human neutrophils in vitro and in vivo

Abstract

The leucocyte adhesion molecule-1 (LAM-1) is the human homologue of the murine peripheral lymph node homing receptor, MEL-14, and might play a crucial role in neutrophil localization at inflammatory sites. We have reported previously that recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates or enhances several neutrophil functions in vivo, as well as in vitro. To further explore the possible role of G-CSF in inflammation we studied the effect of rhG-CSF on the surface expression of LAM-1 on human neutrophils, both in vitro and in vivo. The expression of LAM-1 by human neutrophils was investigated by indirect immunofluorescence using flow cytometry and monoclonal antibodies anti-Leu-8 and TQ1. A whole blood analysis was performed to minimize in vitro manipulation. Most circulating human neutrophils expressed LAM-1 on the cell surface. Brief exposure of neutrophils to rhG-CSF in vitro decreased the surface expression of LAM-1. rhG-CSF down-regulated neutrophil LAM-1 expression in a time- and dose-dependent manner. Neutrophils from healthy volunteers and from patients who were receiving rhG-CSF exhibited a decreased expression of LAM-1 after rhG-CSF administration, and the expression thereafter returned or overshot the pretreatment level after stopping rhG-CSF administration. These findings indicate that rhG-CSF down-regulates the surface expression of LAM-1 on human neutrophils in vivo, as well as in vitro, and G-CSF might participate in neutrophil-endothelial cell interaction in inflamed tissue.

Circulating Granulocyte Colony-Stimulating Factor, C-X-C, and C-C Chemokines in Children with Escherichia Coli O157:H7 Associated Hemolytic Uremic Syndrome

“…This is also in agreement with previous data from our group showing that children with D ϩ HUS have abnormally decreased circulating levels of soluble L-selectin (19). The latter is down-regulated by G-CSF on CD34-positive hematopoietic progenitors (43).…”

Hematopoietic Stem Cell Mobilization Therapy Accelerates Recovery of Renal Function Independent of Stem Cell Contribution

“…This binding may ultimately result in transmigration of the leukocyte across the endothelial monolayer and the underlying extracellular matrix into the renal interstitium. Previous reports demonstrate G-CSF-mediated downregulation of L-selectin on neutrophils in humans (29,30) and release of CD11b from granules in vitro (31). In our model, cytokine treatment resulted in downregulation of L-selectin on granulocytes at the day of injury, whereas expression of CD11b was unaltered.…”

Functional features of neutrophils induced by G-CSF and GM-CSF treatment: differential effects and clinical implications

“…Two groups upregulated by several agonists, eg IFN␥, 138,139 TNF␣, 140 G-CSF 73,140 and GM-CSF 73,140 (Table 1). Administration of G-CSF found a significant downregulation of LAM-1 by G-CSF, 48,60 whereas Griffin et al 59 described an unchanged expression to patients with acquired 70,73 and congenital neutropenias 107,110 and to healthy volunteers 70,71 resulted in an after incubation of neutrophils with G-CSF. Interestingly, the affinity of LAM-1 for ligands (eg PPME) is markedly increased increased expression of the CD14 antigen on neutrophils, whereas GM-CSF did not alter the CD14 level.…”