Enhanced generation of reactive oxygen species in monocytes from patients with common variable immunodeficiency

Abstract

SUMMARYMonocyte and macrophage dysfunction may be important for both immunopathogenesis and c!inica! manifestations in subgroups ofpatients with primary hypogammaglobulinaemia. In the present study we examined the ability to generate reactive oxygen species (ROS) in isolated monocytes from these patients by two different methods: superoxide dismutase (SOD) inhibitable cytochrome c reduction by Oi and nitrobiuc tetrazolium (NBT) reduction. Monocytes from patients with common variable immunodeficiency (CVI) demonstrated significantly enhanced ROS generation both unstimulated and stimulated (unopsonized zymosan and phorbol myristate acetate (PMA)). The enhanced oxidative burst response in CV! patients was found both with and without scrum containing medium. Furthermore, serum from CVI patients did significantly enhance the oxidative burst response in monocytes from healthy hlood donors compared with the effect of control serum. The enhanced ROS generation in CVI patients was significantly correlated with elevated serum levels of neopterin, reduced numbers of CD4' lymphocytes in peripheral blood and occurrence of splenomegaly. !n contrast to the CV! group, monocytes from patients with X-linked agammaglobulinaemia (XLA) did not show enhanced ROS generation. The increased oxidative burst response in monocytes frotn CV! patients most probably reflects in vivo activation of these cells. Our observations indicate the presence of a subgroup of CVI patients characterized by chronic immune activation particularly of monocytes. The enhanced ROS generation might be involved in immunopathogenesis (e.g. T cell dysfunction) and in the pathogenesis of clinica! manifestations (e.g. malignancies and autoimmune disorders) in these patients.

Intravenous immunoglobulin replacement induces an in vivo reduction of inflammatory monocytes and retains the monocyte ability to respond to bacterial stimulation in patients with common variable immunodeficiencies

“…Oxidative burst is the process ending with the rapid release of ROS. Previous papers described an increased ROS production by monocytes from CVID [40].…”

“…In parallel to the reduction of CD11b, ROS production slightly decreased after IVIg infusion. This discrepancy might be mainly due to the different stimuli, in that Aukrust et al [40] used non-opsonized zymosan acting via TLR2 [41] and PMA, while we used a physiological stimulus, the opsonized E. coli acting via Fcγ receptor [42] to induce the monocyte respiratory burst.…”

Identity of the immunomodulatory proteins from garlic (Allium sativum) with the major garlic lectins or agglutinins

“…For the NBT assay [25], peritoneal cells (1 × 10 5 cells/ml) were taken in a volume of 100 µL, to which 400 µL of Hank's balanced salt solution (HBSS) containing garlic ImPs (0.1, 1, 10 µg/mL) were added with 0.4% BSA. The samples were preincubated at 37°C for 10 min, and 2 mM NBT (40 µL/tube) was added and further incubated at 37°C for 20 min.…”

“…It contains ∼ 2% protein based on fresh weight, the major proteins present in the bulb being two agglutinins (25 kD; ASA 25 ) and alliinase (110 kD) [4]. In addition to these proteins, the presence of several other proteins such as high molecular weight glycoprotein agglutinin (110 kD; ASA 110 ) [5], the antifungal protein, allivin (13 kD), from round-cloved garlic [6], and the anti-microbial protein, alliumin (13 kD) [7] have been reported in garlic recently.…”

Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation

“…In patients who received intravenous immunoglobulin (IVIG) substitution, typically with an interval of 3-4 weeks, the blood samples were taken immediately before IVIG administration. We have described previously a subgroup of patients (CVIDHyper) characterized by chronic inflammation in vivo as reflected by splenomegaly and increased serum levels of inflammatory markers [13][14][15]. Patients were classified as CVIDHyper if they had splenomegaly (>13 cm on ultrasonographic or CT scan examination) and serum neopterin levels greater than the mean Ϯ 4 standard deviations (s.d.)…”