In vitro effects of 4-hydroperoxycyclophosphamide on the morphology and function of human peripheral blood mononuclear phagocytic cells (macrophages).

Human peripheral blood mononuclear cells were incubated for 1 hr in 4-hydroperoxycyclophosphamide (0.5 to 10.0 micrograms/ml), and the adherent, esterase-positive cells (macrophages) were studied. At 2 hr, a reduction was noted in both latex particle ingestion and Fc gamma receptor binding and phagocytosis. At 24 hr, spreading and pinocytosis were reduced, and cytoplasmic vacuoles developed. This vacuolization represented dilatation of the rough endoplasmic reticulum. These morphological and functional changes occurred with 4-hydroperoxycyclophosphamide concentrations which did not reduce viability or produce detectable DNA alkylation. This effect on macrophages may offer a mechanism whereby low-dosage cyclophosphamide could modify the immune response.