Neutrophilic granulocytosis following lead acetate in female mice

Lead induces an abrupt neutrophilic granulocytosis with the peak response detected 4 days after treatment. Using the incorporation of tritiated thymidine as an index of neutrophil production, autoradiographic analysis revealed that only about 16% of the total neutrophil increase is associated with a stimulatory effect on production. The remainder of the increase appears to be linked to the panhistotoxic action of lead, promoting migration of neutrophils from reserve sites in the wake of tissue damage.     

Regulation of neutrophil trafficking from the bone marrow

Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation. This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed.     

Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors

Caffeine is the most widely used drug in the world and acts mainly through antagonism of the effects mediated by the adenosine receptor subtypes A1, A2A, A2B and A3. We determined whether repeated caffeine administration at different doses and for different periods of time (400 or 600 mg/day for 1 week and 400 mg/day for 2 weeks) alters human neutrophil A2A adenosine receptor density and function. Saturation binding assays showed an increase in affinity (K(D)) and density (B(max)) of A2A adenosine receptors after caffeine intake. These changes were accompanied by increases in cAMP accumulation and decreases in superoxide anion production after stimulation of the A2A receptor subtype using the agonist 5'-N-ethylcarboxamidoadenosine (NECA). Binding and functional changes of A2A receptors returned to baseline after 48 h of caffeine withdrawal. The findings are consistent with a potential anti-inflammatory effect of caffeine mediated by neutrophil A2A receptors.     

Surface molecules regulating rolling and adhesion to endothelium of neutrophil granulocytes and MDA-MB-468 breast carcinoma cells and their interaction

The extravasation of leukocytes and tumor cells is a multi-step process with the involvement of various adhesion molecules depending on the three steps rolling, adhesion, and diapedesis. We have developed an in vitro model, by which we investigated the rolling and adhesion of neutrophil granulocytes and MDA-MB-468 human breast carcinoma cells to lung endothelial cells under physiological flow-conditions. We found that norepinephrine had an inhibitory function on the fMLP-promoted adhesion of neutrophil granulocytes due to a down-regulation of β2-integrin. Furthermore, neutrophil granulocytes serve as linking cells for the interaction of the MDA-MB-468 cells with the endothelium, which are both β2-integrin negative, but express the β2-integrin ligand ICAM-1. In addition, we show here that N-cadherin is up-regulated on the endothelial cells and on neutrophil granulocytes in response to fMLP. This up-regulation resulted in a significant increase of adherent MDA-MB-468 cells, which are also N-cadherin positive. Received 3 September 2007; received after revision 17 October 2007; accepted 22 October 2007     

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.     

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.     

The effect of cobra venom factor (CVF) activation of the complement cascade on leukocyte circadian variation in the rat

Summary Administration of cobra venom factor (CVF) at different time periods over a 24-h-period produced a leukocytic response which varied according to the time of day the factor was given. The resulting leukocytic circadian rhythm was achieved by a marked variation and increase in the neutrophil population.This study was supported by U. S. P. H. S. Grant No. HL 16769 and Grant No. AI 09169.     

Volume-dependent regulation of the respiratory burst of activated human neutrophils

The effect of incubation medium osmolality on the respiratory burst of human neutrophils was studied using luminol-dependent chemiluminescence (CL) as an indicator of burst activity. Neutrophils were stimulated with N-formyl-Met-Leu-Phe (FMLP), phorbol-12-myristate-13-acetate (PMA), the calcium ionophore A23187, thermoaggregated IgG (IgG_n), and opsonized zymosan (OZ). It was shown that increasing the osmolality of the incubation medium from 320 up to 420 mosM decreased the A231870 and OZ-induced CL responses by 90%. Under the same conditions PMA-, FMLP- and IgG_n-induced CL responses were decreased by 40–60%. A decrease of osmolality to 200 mosM resulted in a 2–3 fold decrease of the A23187-, PMA- and FMLP-induced CL and in a 60–80% increase of OZ- and IgG_n-induced CL. It is suggested that osmolality-mediated alteration of cell volume is an important mechanism for regulating neutrophil activity.     

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.     

Production of urea during mixed leukocyte culture (MLC). Effect of presensitization by a skin allograft]

An increased production of urea has been demonstrated during mixed cultures between allograft donor and recipient leukocytes. This phenomenon may also be observed during primary MLC (i.e, without previous allograft) but to a lesser degree. This increased production of urea during MLC results from an increase of arginase activity in spleen cell population(s) resulting in an increased arginine transformation into urea and ornithine, as demonstrated by the release of an amount of ornithine equivalent to that of urea in the culture supernatant.     

Gene amplification in oocytes of the rove beetle Creophilus maxillosus (Staphylinidae, Coleoptera-Polyphaga).

The extra-DNA body was found, for the first time, in oocytes of an insect with telotrophic ovary. Dispersion of this body is accompanied by an enormous increase of nuclear volume and production of multiple nucleoli. It is suggested that the extra-DNA contains a huge mass of nucleolus organizers.     

Melatonin biosynthesis in the mammalian pineal gland

Rhythmic production of melatonin by the mammalian pineal occurs in response to noradrenergic stimulation which produces a cascade of biochemical events within the pinealocyte. In the rat, massive changes in NAT activity result from an increase in intracellular c-AMP levels produced by a synergistic interaction whereby an alpha 1 activation amplifies beta-adrenergic stimulation. The intracellular events mediating this effect are described. A major aspect of the temporal control of melatonin production is the programmed down-regulation of responses to noradrenergic stimulation once the initial surge of c-AMP is produced. Noradrenergic activation of the gland also influences other enzymic functions, including tryptophan hydroxylase and HIOMT activities, and produces a dramatic increase in intracellular c-GMP levels. Other neurotransmitters and neuropeptides, e.g. VIP, may also influence pineal function and comparisons are made between the rat, the subject of the bulk of experimental studies, and other species.     

Gene amplification in oocytes of the rove beetleCreophilus maxillosus (staphylinidae,coleoptera-polyphaga

Summary The extra-DNA body was found, for the first time, in oocytes of an insect with telotrophic ovary. Dispersion of this body is accompanied by an enormous increase of nuclear volume and production of multiple nucleoli. It is suggested that the extra-DNA contains a huge mass of nucleolus organizers.This research was supported in part by funds from the Cytobiology Committee of the Polish Academy of Science.     

Effects of increased intracellular Ca2+ on cyclic nucleotides production by liver tissue

Summary During hepatointoxication, the increase of intracellular Ca²⁺ is accompanied by an increase of cAMP. This reversible phenomenon suggests that the production of cAMP is likely to be a response of the cell in order to activate the exclusion of Ca²⁺.This work was supported by a grant from the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen.     

Relation between stimulus intensity and neutrophil chemotactic response

Summary The effect of chemotactic peptides which lack chemokinetic activity has been investigated. The neutrophil response is proportional to the logarithm of the stimulus intensity, or alternatively a power function with an exponent of 0.3. Equal responses are obtained for equal ratios between the peptide concentration in the lower compartment and the threshold concentration. The significance of Weber-Fechner's law in leucocyte chemotaxis is discussed.We thank Miss B. Zanolari, Mrs M. Marti, Mrs Hauck and Mr Dietz for excellent technical assistance. This work was supported by the Swiss National Foundation for Scientific Research.     

Histamine production in mixed culture between allograft donor and recipient lymphocytes]

An increased production of histamine has been demonstrated during mixed cultures between allograft donor and recipient lymphocytes. This phenomenon could result from the action of a non-dialysable factor released by recipient cells in the presence of donor cells. This factor is able to increase histamine production from normal spleen cells. Little or no increase in histamine production is found during primary and mixed lymphocyte cultures (without previous allograft).     

Changes of profiles of neutrophil granulocytes induced with the administration of L-DOPA and prednisolone

Morphological changes of granulocytes following combined treatment with L-DOPA and prednisolone were elucidated at the electron microscopic level. Neutrophil granulocytes exhibited marked changes in their surface as evidenced by scanning electron microscope. It is suggested that neutrophil granulocytes are sensitive to some biogenic amines.     

Regulation of phagocyte migration and recruitment by Src-family kinases

Src-family kinases (SFKs) regulate different granulocyte and monocyte/macrophage responses. Accumulating evidence suggests that members of this family are implicated in signal transduction pathways regulating phagocytic cell migration and recruitment into inflammatory sites. Macrophages with a genetic deficiency of SFKs display marked alterations in cytoskeleton dynamics, polarization and migration. This same phenotype is found in cells with either a lack of SFK substrates and/or interacting proteins such as Pyk2/FAK, c-Cbl and p190RhoGAP. Notably, SFKs and their downstream targets also regulate monocyte recruitment into inflammatory sites. Depending on the type of assay used, neutrophil migration in vitro may be either dependent on or independent of SFKs. Also neutrophil recruitment in in vivo models of inflammation may be regulated differently by SFKs depending on the tissue involved. In this review we will discuss possible mechanisms by which SFKs may regulate phagocytic cell migratory abilities.     

Changes of profiles of neutrophil granulocytes induced with the administration of L-DOPA and prednisolone

Summary Morphological changes of granulocytes following combined treatment with L-DOPA and prednisolone were elucidated at the electron microscopic level. Neutrophil granulcytes exhibited marked changes in their surface as evidenced by scanning electron microscope It is suggested that neutrophil granulocytes are sensitive to some biogenic amines.