A possible preferential inhibition of chemotaxis of polymorphonuclear neutrophils by a chemical modification.

The modification of neutrophils with amino group blocking reagents of different chemical specificities showed that dansyl chloride caused inhibition of chemotaxis without suppression of random movement. Dansylated neutrophils, like control cells, ingested bacteria. Neither the stimulated cyanide-insensitive respiration, nor lactate production during phagocytosis, was affected significantly by dansylation as compared with the inhibition of directed movement.     

The effect of halothane on in vitro human neutrophil chemotaxis

Summary Increasing concentrations of halothane were shown to sequentially inhibit directed (chemotactic) and random movement of human peripheral blood neutrophils. No influence on neutrophil movement was apparent at clinically important concentrations, halothane may effect neutrophil microtubule and actomyosin microfilament systems.Acknowledgments. We thank Mr Lous Matej for his skillful technical assistance.     

Neutrophil uptake of nitrogen-bisphosphonates leads to the suppression of human peripheral blood γδ T cells

Nitrogen-bisphosphonates (n-BP), such as zoledronate, are the main class of drugs used for the prevention of osteoporotic fractures and the management of cancer-associated bone disease. However, long-term or high-dose use has been associated with certain adverse drug effects, such as osteonecrosis of the jaw and the loss of peripheral of blood Vγ9Vδ2 T cells, which appear to be linked to drug-induced immune dysfunction. In this report we show that neutrophils present in human peripheral blood readily take up zoledronate, and this phenomenon is associated with the potent immune suppression of human peripheral blood Vγ9Vδ2 T cells. Furthermore, we found this zoledronate-mediated inhibition by neutrophils could be overcome to fully reconstitute Vγ9Vδ2 T cell proliferation by concomitantly targeting neutrophil-derived hydrogen peroxide, serine proteases, and arginase I activity. These findings will enable the development of targeted strategies to mitigate some of the adverse effects of n-BP treatment on immune homeostasis and to improve the success of immunotherapy trials based on harnessing the anticancer potential of peripheral blood γδ T cells in the context of n-BP treatment.     

Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences

Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research.     

Peroxidase activity of neutrophil granules in two cases of congenital myeloperoxidase deficiency]

The neutrophils and monocytes of two patients with hereditary myeloperoxidase deficiency lacked myeloperoxidase activity as determined by light and electron microscopic cytochemical staining. Using Graham-Karnovsky media, azurophils of neutrophils were devoid of peroxidase whereas all eosinophilic and basophilic granules exhibited normal peroxidase activity. After incubation in alkaline diaminobenzidine media which stains the catalase of microperoxisomes, some small granules were seen to be strongly stained in both immature and mature neutrophils. These small granules were distinct from all other neutrophilic granules which lacked a positive reaction. Only, in the presence of cyanide or aminotriazole, peroxidatic activity was also detected in some ellipsoid azurophils. This observation suggests that these substances activated an oxidase whose nature is discussed.     

Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro.

We measured the effects of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the adherence of human neutrophils by using a dacron fiber system to assay the adhesive ability of neutrophils. rhG-CSF enhanced neutrophil adherence to dacron fibers. N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced neutrophil-neutrophil interaction (neutrophil aggregation) in addition to neutrophil-dacron interaction, whereas rhG-CSF did not cause neutrophil aggregation. These results indicated that rhG-CSF increases the adhesive ability of neutrophils without neutrophil-neutrophil interaction, and the action of rhG-CSF in neutrophil activation is different from the neutrophil activation caused by fMLP.     

Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro

Summary We measured the effects of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the adherence of human neutrophils by using a dacron fiber system to assay the adhesive ability of neutrophils. rhG-CSF enhanced neutrophil adherence to dacron fibers. N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced neutrophil-neutrophil interaction (neutrophil aggregation) in addition to neutrophil-dacron interaction, whereas rhG-CSF did not cause neutrophil aggregation. These results indicated that rhG-CSF increases the adhesive ability of neutrophils without neutrophil-neutrophil interaction, and the action of rhG-CSF in neutrophil activation is different from the neutrophil activation caused by fMLP.     

Activation of neutrophils by a chemically separated but optically coupled neutrophil population undergoing respiratory burst

Neutrophils from pig blood were used as a model system to investigate the optical communication between cells. It was found that neutrophils stimulated to undergo respiratory burst can activate a second, chemically separated, but optically coupled population of neutrophils. The response of the latter was visualized as a temporary rising of their low-level chemiluminescence and an enhanced generation of superoxide radicals detected by both the reduction of ferricytochrome c and spin trapping. The results provide evidence that a long-range optical coupling of biological significance between living cells exists.     

Priming effect of vasoactive intestinal peptide on the respiratory burst of neutrophils non-mediated by plasma membrane receptors

Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils in response to phorbol myristate acetate. Maximal and half-maximal effects were achieved at 10 and 0.5 nM VIP respectively. The absence of plasma membrane receptors to VIP in neutrophils suggests that priming of the respiratory burst should be considered as a side effect of VIP. However, from the above indicated concentration range, the priming of the neutrophil by VIP cannot be considered as a pharmacological effect. The enhancement of the formation of reactive oxygen metabolites by VIP may be important in the pathology of VIP-producing tissues.     

Neutrophils are mediators of antiviral immunity.

The paper presents evidence that polymorphonuclear neutrophils upon stimulation with herpesvirus-induced antigens release a material inhibitory to virus infection. The material does not appear to be identical to type I or II interferon.     

Contribution of the Na+/K+-pump to the membrane potential

The inward movement of sodium ions and the outward movement of potassium ions are passive and the reverse movements against the electrochemical gradients require the activity of a metabolism-driven Na+/K+-pump. The activity of the Na+/K+-pump influences the membrane potential directly and indirectly. Thus, the maintenance of a normal electrical function requires that the Na+/K+-pump maintain normal ionic concentrations within the cell. The activity of the Na+/K+-pump also influences the membrane potential directly by generating an outward sodium current that is larger when the Na+/K+-pump activity is greater. The activity of the Na+/K+-pump is regulated by several factors including the intracellular sodium concentration and the neuromediators norepinephrine and acetylcholine. The inhibition of the Na+/K+-pump can lead indirectly to the development of inward currents that may cause repetitive activity. Therefore, the Na+/K+-pump modifies the membrane potential in different ways both under normal and abnormal conditions and influences in an essential way many cardiac functions, including automaticity, conduction and contraction. Key words. Active transport of ions; cardiac tissues; electroneutral and electrogenic Na+/K/-pump; control of Na+/K+-pump; normal and abnormal electrical events.     

Dependence on the lipophilicity of maleimide derivatives in their inhibitory action upon chemotaxis in neutrophils.

Modification of polymorphonuclear neutrophils by a series of maleimide derivatives with various degrees of lipophilicity and hydrophilicity indicated that hydrophilic reagents had little effect on chemotaxis, whereas the degree of the inhibitory effect of lipophilic reagents on the chemotaxis was parallel to the degree of their lipophilicity.     

Inhibition of neutrophil-mediated cytotoxicity by alpha 2 macroglobulin

Highly purified human alpha 2 macroglobulin (1.2--10 mg/ml) was shown to inhibit phytohemagglutinin-induced or antibody-induced lysis of chicken erythrocytes by polymorphonuclear neutrophils. Inhibition was not associated with impaired contact between effector and target cells but rather with the antiprotease activity of alpha 2 macroglobulin.     

Destruction of virus infected cells by neutrophils and complement

The paper describes an antibody independent mechanism of cytotoxicity whereby virus infected but not uninfected cells are destroyed by the combined presence of neutrophils and complement.     

Production of superoxide by neutrophils

Cellular and Molecular Life Sciences - Oxygen uptake by neutrophils has been stimulated by particulate serum-treated-zymosan (STZ) and soluble N-formylmethionyl-leucyl-phenylalanine (FMLP) in the...     

Studies on the relationships between biotin and the behaviour of B and T lymphocytes in the guinea-pig

Summary In biotin-deficient guinea-pigs the number of circulating neutrophils is increased; lymphocytes carrying B and T markers are decreased. Incubation with biotin increases significantly the number of lymphocytes carrying B and T markers, from biotin-deficient guinea-pigs; no increase was observed when the lymphocytes from normal guinea-pigs were incubated.     

Chemotaxis is not a special case of haptotaxis

Serum peptides containing classical anaphylatoxin (CAT) produce marked chemotatic orientation of human neutrophil granulocytes without modifying cell attachment to the substratum. Furthermore gradients of adhesion produced with gammaglobulins fail to induce morphological orientation of neutrophils. The results suggest that chemotaxis is not a special case of haptotaxis.     

Neutrophils are mediators of antiviral immunity

Summary The paper presents evidence that polymorphonuclear neutrophils upon stimulation with herpesvirus-induced antigens release a material inhibitory to virus infection. The material does not appear to be identical to type I or II interferon.The work was supported by the Medical Research Council of Canada. We thank Terry Beskorwayne for technical assistance.     

Peptidylarginine deiminase in rat and mouse hemopoietic cells

Peptidylarginine (protein-L-arginine) deiminase activities have been demonstrated in extracts of rat and mouse peritoneal macrophages, bone marrow cells, splenic adherent cells, neutrophils, and mouse monocyte/macrophage cell lines. The enzyme in these cells is indistinguishable from the skeletal muscle enzyme with respect to immunochemical properties.