Studies of neutrophil and monocyte oxidative responses in polycythaemia vera and related myeloproliferative disorders

Summary. We have previously reported that polymorphonuclear granulocyte (PMN) chemiluminescence (CL) and superoxide anion production are abnormally low in patients with polycythaemia vera (PV) after simulation with n-formylmethionyl-leucyl-phenylalanine (fMLP). but normal when elicited by phorbol myristate acetate (PMA). This study documents that both fMLP and PMA induced CL was normal in PMN from patients with chronic myelogenous leukaemia (CML) and essential thrombocythaemia (ET). Furthermore, we monitored intracellular hydrogen peroxide (H₂O₂) production in PMN and monocytes from patients with PV, CML and ET by flow cytometry. H₂O₂) production in resting and PMA-stimulated cells was normal in all diseases. So also was fMLP induced H₂O₂ generation in ET PMN and monocytes. In contrast, fMLP-induced H₂O₂ production was significantly lower both in PV PMN (1.8 ± 0.7 mean fluorescence intensity units in PV compared to 8.4 ± 3.4 in healthy controls; P < 0.02), and in PV monocytes (0.3 ± 0.5 compared to 2.5 ± 0.7 in controls; P < 0.02). A less pronounced reduction of fMLP stimulated H₂O₂ production was noted in CML PMN (3.8 ± 3.1 compared to 8.4 ± 3.4 in controls; P < 0.05), and monocytes (1.3 ± 0.6 compared to 2.5 ± 0.7 in controls: P < 0.05). The reduction of H₂O₂ generation in PV and CML PMN was not attributed to subpopulations of less responsive cells. However, one ET and one CML patient showed a subpopulation of less responsive PMN. Thus intracellular H₂O₂ (as well as extracellular release of superoxide ions) is reduced in fMLP-stimulated PV PMN and monocytes but normal after PMA stimulation, a phenomenon that is not consistently found in other myeloproliferative disorders.