Chantal Damais

Nitric oxide production by human monocytes: evidence for a role of CD23

Nitric oxide (NO) appears to be an important and pleiotropic bioregulator of immune responses. The existence of the NO synthase (NOS) pathway in human monocytes/macrophages remains a subject of controversy, despite an increasing number of reports suggesting that human monocytes produce NO in vitro in response to various stimuli. Here, Bernard Dugas and colleagues consider the arguments supporting these conclusions, with particular emphasis on the results obtained by ligation of the low-affinity IgE receptor (Fcepsilon RIIb/CD23b).

Recombinant human interleukin-1 beta primes human polymorphonuclear leukocytes for stimulus-induced myeloperoxidase release

Recombinant human Interleukin‐1 (rhlL‐1) β was found to enhance stimulus‐induced granule exocytosis from human polymorphonuclear leukocytes (PMNs). PMNs were incubated with rhlL‐1β and then stimulated with either heat‐aggregated IgG (Hagg) or N‐formyhmethionyl leucylphenylalanine (FMLP). The release of the azurophil enzyme myeloperoxidase (MPO) was measured. Low concentrations of stimuli (10 μg/ml Hagg, 2.5 x 10‐9 M FMLP) did not stimulate degranulation in the absence of rhlL‐1β. However, such concentrations elicited marked degranulation from PMNs preincubated with rhlL‐1β (0.2‐100 ng/ml). The enhancement of degranulation was dependent on the concentration of rhIL‐1β employed and on the period of incubation. In other experiments, the effect of rhlL‐1β on the PMN oxidative response was determined. rhlL‐1β did not directly stimulate the production of superoxide anions or enhance the oxidative response to Hagg or FMLP. It is suggested that in rheumatoid joints, IL‐1β may potentiate PMN degranulation, but not their oxidative response.

Nitric Oxide Production in Human Macrophagic Cells Phagocytizing Opsonized Zymosan: Direct Characterization by Measurement of the Luminol Dependent Chemilurninescence

When differentiated into mature macrophages by the combination of all-trans retinoic acid and 1, 25-dihy-droxyvitamin D3, the human promonocytic cell lines U937 and THP-1 expressed inducible nitric oxide syn-thase (iNOS) transcripts. During their differentiation, the cells acquired the capacity to produce not only superoxide anion (O2−) but also nitric oxide (NO) in response to IgG (or IgE)-opsonized zymosan. The inhibitors of the iNOS pathway, aminoguanidine and NG-monomethyl-L-arginine (L-NMMA), suppressed the production of .NO and enhanced the steady-state concentration of O2− determined. Conversely, super-oxide dismutase (SOD) scavenged the O2− released and increased the NO-derived nitrite concentration detected. These data suggested a possible interaction between O2− and NO. In differentiated U937 (or THP-1) cells, IgG or IgE-opsonized zymosan induced a strong time-dependent luminol-dependent chemiluminescence (LDCL), which was abroated by SOD and partially inhibited by aminoguanidine or L-NMMA. Sinc...

Beta 2-adrenoceptor agonists regulate the IL-4-induced phenotypical changes and IgE-dependent functions in normal human monocytes.

The β 2‐adrenoceptor agonists salbutamol and fenoterol were tested for their regulatory effects on human monocyte phenotype and functions, either alone or in combination with interleukin‐4 (IL‐4). These drugs enhanced in a dose‐dependent manner the IL‐4‐induced membrane and mRNA expression of the low‐affinity receptor for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form, sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic β 2‐chain (CD18) of the leukocyte functional antigen (LEA1) family. This effect appeared to be restricted to CD11b (CR3) and CD11c (gp 150–95), because CD11a (LFA‐1α chain) was not modified, β 2‐Adrenoceptor stimulation was also found to potentiate the effect of IL‐4 on CD11b, CD11c, and CD18 expression. In contrast, these agents alone did not alter the level of major histocompatibility complex class II and CD14 antigens or modify their respective up‐ and down‐regulation by IL‐4. Ligation of CD23 on IL‐4‐preincubated (CD23*) monocytes with IgE/anti‐IgE immune complexes induced the release of free radicals nitric oxide and of the proinflammatory mediators IL‐6 and thromboxane B2 (TxB2). Addition of salbutamol, inactive alone, potentiated the generation of superoxide anion and of nitric oxide generation, as well as the production of IL‐6 and TxB2 triggered by CD23 ligation. These results indicate that β 2‐adrenoceptor stimulation potentiates in vitro the IL‐4‐induced phenotypical and functional changes on monocytes and suggest that such an interaction could occur in IgE‐dependent immune reactions. J. Leukoc. Biol. 55: 313–320; 1994.

An increase in intracellular pH is a general response of promonocytic cells to differentiating agents.

Intracellular pH (pHi) was measured in HL60 and U937 cells before and after differentiation into monocyte‐macrophage like cells. 12‐O‐Tetradecanoyl phorbol‐13‐acetate (PMA), butyrate, interferon, retinoic acid and 1,25‐dihydroxyvitamin D3 all increased pHi. The increases elicited were rapid with PMA, much slower with retinoic acid and interferon and still slower with 1,25‐dihydroxyvitamin D3. Increases in pHi are due to an activation of the Na+/H+ exchange system. High pHi values are unlikely to serve as an early intracellular signal for initiating monocytic differentiation.

Opposite effect of interferon-γ on PGE2 release from interleukin-1-stimulated human monocytes or fibroblasts

Stimulated monocytes produce prostaglandins (PGE2) in response to lipopolysaccharide (LPS), Muramyl dipeptide (MDP) or Interleukin-1 (IL-1). This response could be modulated in different ways by Interferon-gamma (IFN-gamma). This lymphokine, known to potentiate IL-1 production by LPS- or MDP-stimulated monocytes, suppressed different Il-1 activities such as PGE2 release by the same cells. By contrast, an impairement of suppression by IFN-gamma was evidenced in rIL-1 beta-induced PGE2 release from human dermal fibroblasts. Salmon calcitonin (sCT), another inhibitor of IL-1-induced bone resorption, was able to prime monocytes to potentiate PGE2 elaboration by LPS, but failed to modulate PGE2 liberation from either rIL-1 beta-stimulated monocytes or fibroblasts.

Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections

HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation. This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus. In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO). Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased. This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients. In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients. These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection. This overproduction of NO could play an important role in the development of AIDS symptoms and signs.