STUDIES OF NEUTROPHIL AND MONOCYTE OXIDATIVE RESPONSES IN POLYCYTHEMIA-VERA AND RELATED MYELOPROLIFERATIVE DISORDERS

We have previously reported that polymorphonuclear granulocyte (PMN) c hemiluminescence (CL) and superoxide anion production are abnormally l ow in patients with polycythaemia vera (PV) after simulation with n-fo rmyl-methionyl-leucyl-phenylalanine (fMLP), but normal when elicited b y phorbol myristate acetate (PMA). This study documents that both fMLP and PMA induced CL was normal in PMN from patients with chronic myelo genous leukaemia (CML) and essential thrombocythaemia (FT). Furthermor e, we monitored intracellular hydrogen peroxide (H2O2) production in P MN and monocytes from patients with PV, CML and ET by now cytometry. H 2O2 production in resting and PMA-stimulated cells was normal in all d iseases. So also was fMLP induced H2O2 generation in ET PMN and monocy tes. In contrast, fMLP-induced H2O2 production was significantly lower both in PV PMN (1.8 +/- 0.7 mean fluorescence intensity units in PV c ompared to 8.4 +/- 3.4 in healthy controls; P < 0.02), and in PV monoc ytes (0.3 +/- 0.5 compared to 2.5 +/- 0.7 in controls; P < 0.02). A le ss pronounced reduction of fMLP stimulated H2O2 production was noted i n 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 attri buted to subpopulations of less responsive cells. However, one ET and one CML patient showed a subpopulation of less responsive PMN. Thus in tracellular H2O2 (as well as extracellular release of superoxide ions) is reduced in fMLP-stimulated PV PMN and monocytes but normal after P MA stimulation, a phenomenon that is not consistently found in other m yeloproliferative disorders.