Activated phenotype in neutrophils and monocytes from patients with primary proliferative polycythaemia.

Abstract

Aim-To investigate whether monocytes and neutrophils from patients with primary proliferative polycythaemia (PPP) exhibit increased expression of markers of cell activation and, if so, whether they are associated with the phagocytic activity of these cells and concentrations of circulating cytokines. Methods-Expression of CD11b, CD14, CD18, and CD64 on monocytes and neutrophils was assessed by flow cytometry. Phagocytosis was analysed using immunoglobulin opsonised Escherichia coli. Serum concentrations of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) were determined by bioassays, and interferon-y (IFN-y) by enzyme linked inumunosorbent assay (ELISA). Results-Patients with PPP (n = 18), when compared with normal subjects (n= 10), had increased percentages of CD64 + monocytes (52% v 36%) and neutrophils (42% v 11%) and of CD14+ neutrophils (36% v 18%) . Monocytes from patients with PPP exhibited increased expression of CD64 (47 v 26) and of CD11b (65 v 36). These abnormalities were not found in patients with secondary (n = 8) or apparent (n = 13) polycythaemia. The percentage of neutrophils undergoing phagocytosis was higher in patients with PPP (mean 64%; n = 6) than in normal subjects (mean 42%; n=5). G-CSF, GM-CSF and IFN-y concentrations in patients' serum samples were comparable with normal; M-CSF was not detected in any of the samples.There was no correlation between cytokine concentrations and the expression of CDl1b, CD14, CD18, and CD64 on patients' phagocytes. Conclusions-Increased expression of CDllb and CD64 by monocytes, increased percentages of CD14+ and CD64+ neutrophils and the high phagocytic activity of neutrophils suggests that these celis are activated in vivo in patients with PPP. The phenotypic changes of PPP phagocytes were not associated with increased concentrations of circulating cytokines and probably reflect intrinsic abnormalities within the neoplastic PPP clone. (3 Clin Pathol 1995;48:525-530)

Increased CD11/CD18 Expression and Altered Metabolic Activity on Polymorphonuclear Leukocytes from Patients with Polycythemia vera and Essential Thrombocythemia

“…In agreement with Westwood et al [6]the expression of CD11b/CD18 glycoproteins in PMNs of patients with PV was increased. Furthermore, we found that this feature is extended to patients with ET, suggesting that PMNs could share a similar defect in both groups of patients.…”

“…This phenotypic change could be the consequence of previously suggested mechanisms including intrinsic abnormalities within the neoplastic clone [6]. Secondary changes may also be induced by hydroxyurea [11], but in our study the expression of integrins CD11/CD18 was only slightly superior in patients that were taking hydroxyurea.…”

“…Neutrophil dysfunction is well documented in chronic myeloid leukemia [1, 2]while contradictory results of phagocytic cell function have been reported in other myeloproliferative syndromes. Several authors have found that polymorphonuclear leukocytes (PMNs) in polycythemia vera (PV) show normal, even enhanced, phagocytosis, adhesion and metabolic activity [3, 4, 5, 6], whereas others have found a defective oxidative metabolism and myeloperoxidase activity [7, 8, 9]. Recent studies on essential thrombocythemia (ET) also showed discrepant results [10, 11].…”

Blood cell activation in myeloproliferative neoplasms

“…[3][4][5][6][7][8][9] However, in none of these studies was a comparison made between patients with myeloproliferative disease with and without thrombosis. Arellano-Rodrigo et al first analyzed leukocyte and platelet activation in ET patients with and without thrombosis, showing an increased percentage of platelets that expressed P-selectin, as well as overexpression of the monocyte CD11b antigen in patients with thrombosis, 10 which suggests that the activation of the platelets and leukocytes (and, notably, the monocytes) could be involved in the genesis of the thrombosis of this disease ( Table 1).…”

Serum levels of granulocyte colony-stimulating factor in JAK2 V617F -positive vs. negative erythrocytosis

“…The detected values of serum G‐CSF in the patients with PV were within the normal range (Westwood et al. , 1996).…”