Motility of rhG‐CSF‐induced neutrophils in patients undergoing chemotherapy: evidence for inhibition detected by image analysis

Abstract

The motility of circulating neutrophils from seven patients affected by intermediate and high-grade non-Hodgkin's lymphoma was investigated before and after rhG-CSF administration (5 micrograms/kg/d for 5 d subcutaneously) in the course of chemotherapy. Random motility and bacterial lipopolysaccharide-induced chemotaxis were studied by the micropore filter technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer-assisted image processing system, capable of giving several parameters about the kinetics of cell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was found. The kinetics of cell migration showed that the cells maintained the typical gaussian pattern of random motility. On the contrary, neutrophils were found to have lost the typical stimulated migration peak. These findings are consistent with a rhG-CSF-induced impairment of the directional movement, rather than of the ability of moving at random. These effects were found in patients who, in the same experimental conditions, had displayed an enhanced phagocytosis and phagocytosis-associated chemiluminescence along with an enhanced CD32 expression, not due to an aspecific cell manipulation. Two hypotheses may be taken into account: (i) an increased adhesiveness due to a direct or an indirect activity of the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh-GCSF administration can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to investigate the optimum dosage both to correct neutrophil number and preserve neutrophil functional activities.

Derivation of functional mature neutrophils from human embryonic stem cells

“…The effect of G-CSF on the random migration of neutrophils is controversial; random migration increases in vitro when neutrophils are stimulated by G-CSF, 36 whereas neutrophils obtained from G-CSF-treated patients with nonmyeloid malignancies show decreased random migration and chemotaxis. 37,38 Our in vitro experiment with PB-Neu(Gϩ)'s and PB-Neu(GϪ)'s replicated the former result. Nevertheless, hESCNeu's showed relatively low random migration despite stimulation with G-CSF, while maintaining almost normal fMLP-induced chemotaxis.…”

Differences in functional activity and antigen expression of granulocytes primed in vivo with filgrastim, lenograstim, or pegfilgrastim

“…Single‐formulation studies evaluating the effect of lenograstim 9,10 or filgrastim 8,11 , 12 showed impaired chemotaxic activity of the granulocytes. Nevertheless, in a previous comparative study, 13 there was evidence that lenograstim affected chemotaxic properties less than filgrastim.…”

“…There is evidence for differences between these three G‐CSF formulations in modifying neutrophil functions. Generally, chemotactic properties, which are essential for granulocyte function in host defense, are known to be impaired after treatment with G‐CSF 8‐12 . Azzara and coworkers 13 observed that filgrastim reduced chemotaxis more than lenograstim; recently published data attribute this reduced chemotaxis as well as morphological changes after filgrastim to cytoskeletal rearrangements 14 .…”

Neutropenia, Neutrophil Dysfunction, and Bacterial Infection in Patients with Human Immunodeficiency Virus Disease: The Role of Granulocyte Colony-Stimulating Factor

“…These effects include enhancement of adherence, phagocytosis, respiratory burst, and degranulation. Improvement in chemotaxis has been reported by some investigators, although the effect of rG-CSF on this function is unclear [43][44][45][46]. Improvement in other aspects of neutrophil function with rG-CSF administration have also been demonstrated in vitro.…”