Administration of rHuGM‐CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high‐dose chemotherapy

Abstract

Microbicidal and cytocidal products of the respiratory burst and integrin adhesion molecule expression have been studied in monocytes from patients who received rHuGM-CSF during regeneration after high-dose chemotherapy. In this study, administration of rHuGM-CSF after high-dose chemotherapy significantly augmented the secretion of inducible products of the monocyte respiratory burst. Monocyte activation persisted for several weeks after the cessation of GM-CSF therapy. Under in vitro conditions that mimicked gram-negative (LPS) and gram-positive (opsonized Staphylococcus aureus) sepsis, the monocyte responded to such stimulation by exhibiting an enhanced release of hydrogen peroxide at both regeneration and several weeks later (P < 0.001). Similarly, GM-CSF administration significantly augmented the phenotypic expression of the beta 2-integrin adhesion molecules and allowed the leucocyte-specific selectin, LAM-1, and the beta 2-integrins to respond normally to inflammatory stimulation by LPS. We further present evidence that GM-CSF therapy restored the otherwise refractory status of monocytes to inflammatory stimulation that existed in those patients given chemotherapy alone. The restoration of monocyte responsiveness by GM-CSF following high-dose chemotherapy could be a potentially valuable and hitherto not described action of rHuGM-CSF on monocyte function. We conclude that administration of GM-CSF may have the potential for restoring as well as augmenting the anti-microbial and anti-tumour function of the monocyte after high-dose chemotherapy.

The RET receptor tyrosine kinase, but not its specific ligand, GDNF, is preferentially expressed by acute leukaemias of monocytic phenotype and is up-regulated upon differentiation

“…U937 cells induced with a vitamin D 3 /TGF-b combination), in which a more pronounced monocytic differentiation had occurred. Furthermore, as shown here and previously (Gattei et al, 1997a), macrophage activation by GM-CSF, which has been described to upregulate the expression of b2-integrins and ICAM-1/CD54 on circulating monocytes both in vivo and in vitro (Bernasconi et al, 1995;Williams et al, 1995), resulted in a more than 3-fold increase of RET-specific mRNA. Taken together, this data indicated that RET expression in human AML was maturation-associated and probably mirrored the developmental regulation of these genes during physiologic haemopoiesis.…”

Effect of Different Forms of Adenylate Cyclase Toxin ofBordetella pertussison Protection Afforded by an Acellular Pertussis Vaccine in a Murine Model

“…GM-CSF, which is produced by a range of cell types (24), activates immune effector cells (15,51,54), induces the maturation of dendritic cells for increased antigen presentation to promote both Th1 and Th2 immune responses (7,26,47,49,50), and induces the expression of CD11b/CD18 (CR3) receptors found on the surfaces of neutrophil polymorphonuclear leukocytes and monocytes (57). CR3 is a receptor for several B. pertussis virulence-associated factors, including FHA, PRN, and CyaA (13,17,20).…”

Interaction of vitamin D derivatives and granulocyte–macrophage colony-stimulating factor in leukaemic cell differentiation

“…17 It also Since the findings that the intracellular vitamin D receptor plays a role in influencing the functional activity of mature (VDR) is expressed in myeloid cells, 1,2 it has been recognised leukocytes, mediating their immune responses accordingly. 18 that its ligand, 1␣, 25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), is There have been previous reports demonstrating synergistic able to regulate myeloid cell replication and differentiation.…”