MOTILITY OF RHG-CSF-INDUCED NEUTROPHILS IN PATIENTS UNDERGOING CHEMOTHERAPY - EVIDENCE FOR INHIBITION DETECTED BY IMAGE-ANALYSIS

The motility of circulating neutrophils from seven patients affected b y intermediate and high-grade non-Hodgkin's lymphoma was investigated before and after rhG-CSF administration (5 mu g/kg/d for 5 d subcutane ously) in the course of chemotherapy. Random motility and bacterial li popolysaccharide-induced chemotaxis were studied by the micropore filt er technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer-assisted image processin g system, capable of giving several parameters about the kinetics of c ell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was fou nd, The kinetics of cell migration showed that the cells maintained th e typical gaussian pattern of random motility. On the contrary, neutro phils were found to have lost the typical stimulated migration peak. T hese 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 con ditions, had displayed an enhanced phagocytosis and phagocytosis-assoc iated chemiluminescence along with an enhanced CD32 expression, not du e 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 matu ration and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh-GCSF administratio n can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to in vestigate the optimum dosage both to correct neutrophil number and pre serve neutrophil functional activities.