Chemotaxis Term Research Articles

A PARABOLIC–HYPERBOLIC FREE BOUNDARY PROBLEM MODELLING TUMOR TREATMENT WITH VIRUS

We consider a procedure for cancer therapy which consists of injecting replication-competent viruses into the tumor. The viruses infect tumor cells, replicate inside them, and eventually cause their death. As infected cells die, the viruses inside them are released and then proceed to infect adjacent tumor cells. However, a major factor influencing the efficacy of virus agents is the immune response that may limit the replication and spread of the replication-competent virus. The competition between tumor cells, a replication-competent virus and an immune response is modelled as a free boundary problem for a nonlinear system of partial differential equations, where the free boundary is the surface of the tumor. In this model, the immune response equation is a semilinear parabolic equation, including a chemotaxis term which is used to describe the movement of the immune response induced by gradients of the infected cell density. Under the assumption that the chemotactic sensitivity coefficient is small compared with the diffusion coefficient of the immune response, we prove the global existence and uniqueness of the solution of this free boundary problem. For large chemotactic coefficient, the global existence is still open.

Complex pattern formation of marine gradient bacteria explained by a simple computer model

We report on the formation of conspicuous patterns by the sulfide-oxidizing bacterium Thiovulum majus and a recently described vibrioid bacterium. These microaerophilic bacteria form mucus veils on top of sulfidic marine sediment exhibiting regular spaced bacterial patterns (honeycombs, interwoven bands, or inverse honeycombs). A simple qualitative computer model, based on chemotaxis towards oxygen and the ability of the bacteria to induce water advection when attached, can explain the formation of the observed patterns. Our study shows that complex bacterial patterns in nature can be explained in terms of chemotaxis and resource optimisation without involvement of cell–cell signalling or social behavior amongst bacteria.

Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils

The modification of serine/threonine residues on cytoplasmic and nuclear proteins by N-acetylglucosamine (O-GlcNAc) is suggested to play a role in the regulation of a variety of signal transduction pathways. We have previously shown that glucosamine (GlcNH(2)), a metabolic precursor of O-GlcNAcylation, increases (2)O-GlcNAc and enhances motility in neutrophils. Here, we extend this correlation by showing that a mechanistically distinct means of increasing O-GlcNAc, achieved by inhibition of O-GlcNAc removal with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), increases basal cellular motility and directional migration induced by the chemoattractant formyl-methionine-leucine-phenylalanine (fMLP). Furthermore, we demonstrate that O-GlcNAc modulates the activities of signaling intermediates known to regulate neutrophil movement. GlcNH(2) and PUGNAc increase both the basal and fMLP-induced activity of a central mediator of cellular motility, the small GTPase Rac. Phosphoinositide 3-kinase, an important regulator of Rac activity and neutrophil motility, is shown to regulate the signaling pathway on which GlcNH(2) and PUGNAc act. Rac is an important upstream regulatory element in p38 and p44/42 mitogen-activated protein kinase (MAPK) signaling in neutrophils, and these MAPKs are implicated in chemotactic signal transduction. We show that GlcNH(2) and PUGNAc treatment increases p42/44 and p38 MAPK activities and that these increases are associated with activation of upstream MAPK kinases. These data indicate that O-GlcNAcylation is an important signaling element in neutrophils that modulates the activities of several critical signaling intermediates involved in the regulation of cellular movement.

Upregulation of expression of the chemokine receptor CCR5 by hydrogen peroxide in human monocytes.

The objective of this study was to test the hypothesis that an oxidative stress can serve as a signal to regulate the expression of CCR5. When human monocytes were exposed to graded concentration of hydrogen peroxide (H(2)O(2)), CCR5 mRNA levels increased maximally at 4 h of exposure to 200 microM of H(2)O(2) and decreased by 24 h of treatment. Pretreatment of monocytes with the NF-kappaB inhibitor BAY 11-8072 blocked the H(2)O(2)-induced augmentation of CCR5 mRNA expression, suggesting a role for this transcription factor in the regulation of CCR5 expression. CCR5 protein expression on the plasma membrane was also increased by treatment with H(2)O(2,) as assessed by flow cytometry. This was accompanied by enhanced responsiveness of H(2)O(2)-pretreated monocytes to the CCR5 ligand MIP-1beta in terms of chemotaxis and c-fos gene activation. Our results suggest that oxidative stress may indeed modulate the expression of chemokine receptors and thus contribute to regulation of the inflammatory process.

Fractional step methods applied to a chemotaxis model.

A fractional step numerical method is developed for the nonlinear partial differential equations arising in chemotaxis models, which include density-dependent diffusion terms for chemotaxis, as well as reaction and Fickian diffusion terms. We take the novel approach of viewing the chemotaxis term as an advection term which is possible in the context of fractional steps. This method is applied to pattern formation problems in bacterial growth and shown to give good results. High-resolution methods capable of capturing steep gradients (from CLAWPACK) are used for the advection step, while the A-stable and L-stable TR-BDF2 method is used for the diffusion step. A numerical instability that is seen with other diffusion methods is analyzed and eliminated.

SLC/exodus2/6Ckine/TCA4 induces chemotaxis of hematopoietic progenitor cells: differential activity of ligands of CCR7, CXCR3, or CXCR4 in chemotaxis vs. suppression of progenitor proliferation.

Chemokines induce chemotaxis of hematopoietic progenitor cells (HPC), and suppress their proliferation. In this study we report that SLC/ Exodus2/6Ckine/TCA4 (hereafter termed SLC) is a chemoattractant for human CD34+ HPC. SLC mainly induces preferential chemotaxis of macrophage progenitors. We examined the chemotactic activity of CXCR3 ligands on CD34+ HPC because it has been reported that SLC is a potential ligand of CXC chemokine receptor, CXCR3, in addition to a CC chemokine receptor, CCR7. It was found that the CXCR3 ligands, MIG and interferon-gamma inducible protein-10 (IP-10), unlike SLC, did not induce chemotaxis of CD34+ HPC. In this regard, CCR7 ligands (SLC and CKbeta-11), but not IP-10 and MIG, induce actin polymerization in CD34+ cells. On the other hand, CCR7 ligands and CXCR3 ligands, but not the CXCR4 ligand SDF-1, showed inhibitory activity for proliferation of myeloid progenitor cells. Our results suggest that SLC is a potential trafficking factor for HPC, and that chemokines that bind CCR7, CXCR4, and CXCR3 have differential biological activities on HPC in terms of suppression and chemotaxis.

Increased neutrophil chemotaxis in obstructive jaundice: an in vitro experiment in rats.

Changes in neutrophil functions in obstructive jaundice have been poorly understood. An in vitro experimental study was performed to evaluate the effect of obstructive jaundice on the functions of macrophages (secretion of neutrophil chemoattractants) and neutrophils (chemotaxis and superoxide anion generation). Obstructive jaundice was produced in rats by 7 day bile duct ligation. Peripheral neutrophils and peritoneal macrophages were harvested from either normal, sham-ligated or bile duct-ligated rats and supernatants of the monolayers of the respective macrophages were prepared after stimulation with lipopolysaccharide. Neutrophil chemotaxis was evaluated with a modified Boyden method. The supernatant of the bile duct-ligated rat macrophages showed a chemotactic effect on normal rat neutrophils with insignificant difference from the supernatant of the sham-ligated rat macrophages. Chemotaxis of the bile duct-ligated rat neutrophils towards the supernatant of the normal rat macrophages was significantly increased, compared with that of sham-ligated rat neutrophils. Similarly, neutrophils from bile duct-ligated rats showed significantly greater chemotaxis to formyl-methionyl-leucyl-phenylalanine than the sham-ligated rat neutrophils. Superoxide anion generation in response to formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate was significantly increased in the bile duct-ligated rats compared with the sham-ligated rats. The results suggest that the neutrophil is primed in terms of chemotaxis and superoxide anion generation in obstructive jaundice. How these activated neutrophils play a role in the inflammatory response to obstructive jaundice should be evaluated.

The effect of trypsin and chymotrypsinon the chemotaxis and activation of eosinophil

Background : Eosinophilic leukocytes are prominent cellular participants in the pathogenesis of allergic disease and asthma. Chemotaxis is still a very useful method in evaluating the response of human eosinophil to novel modulators. Degranulated mast cells and activated T lymphocytes are responsible for the pathophysiology of asthma and tryptase is one of most important proteases released after activation of mast cells. The purpose of this study was to investigate the actions of trypsin and chymotrypsin on eosinophils in terms of chemotaxis and activation. Method : Eosinophils were isolated by negative immunoselection from the peripheral blood of atopic donors. Chemotaxis was studied by using micro-Boyden chambers and ECP release was assayed by fluoroimmunoassay. Results : Eosinophil showed a chemotactic response to trypsin. Maximal chemotactic response was with trypsin (/HPF) which was comparable to PAP. But chymotrypsin showed no significant chemotactic response to eosinophils. Trypsin at the concentration of 10, 100, induced secretion of ECP, which at the concentration of represented about 2.7 times of the spontaneous rate of release. Soybean protease inhibitor reduced trypsin induced ECP release. Conclusion : Trypsin can induce chemotactic response to eosinophils and activation of eosinophils that can induce secretion of ECP. On the contrary, chymotrypsin showed no direct effect on eosinophils. We propose a role of trypsin on the chemotaxis and activation of eosinophils.

The change of the amount of receptors on the cell surface after differentiation of human granulocyte cell line HL-60

In this study, HL-60, a human granulocyte cell line was differentiated into granulocyte-like cell by DMSO and then the change of the amount of Fc receptors and chemotaxis-associated antigen (TM 316) was examined using monoclonal antibodies and fluorescence analysis of cell sorter. The results showed that the amount of chemotaxis-associated antigen increased slightly and chemotactic activity was poor even after HL-60 was well-differentiated. Fc gamma R I (CD 64) and Fc gamma R II (CD 32) receptors in differentiated HL-60 were slightly recognized. However, there was no Fc gamma R III B (CD 16 b) receptor in differentiated HL-60 cells. Although DMSO induced HL-60 was morphologically similar to peripheral granulocytes, differentiated HL-60 was different from peripheral granulocytes in terms of chemotaxis and surface receptors.

Synergism Between Platelet Activating Factor and C-C Chemokines for Arachidonate Release in Human Monocytes

Monocyte Chemotactic Protein(MCP)-1 and other members of the C-C branch of the chemokine superfamily (RANTES, MIP1α/LD78, and MCP-3) induced, at chemotactic concentrations, the release of [3H]arachidonic acid in prelabeled human monocytes. Arachidonate release was potentiated (2 to 4 fold) in the presence of platelet activating factor (PAF). PAF effect was blocked by a specific receptor antagonist, WEB 2187, and was not present when inactive analogs, PAF inactive enantiomer, or lysoPAF were used. Thus, the synergistic action of PAF with C-C chemokines, in terms of arachidonate release and chemotaxis, is specific for this alkylphospholipid and is receptor mediated. Reciprocal potentiation of PAF and C-C chemokines may be important at sites of inflammation.

A thermodynamical model of cell distributions in the slug of cellular slime mold

A theoretical model is proposed for the formation of cell distribution patterns in the slug stage of the cellular slime mold Dictyostelium discoideum . The equilibrium distribution of two types of cells, prestalk and prespore, is obtained by minimizing the free energy, which is defined in terms of differential chemotaxis, differential cell adhesion and randomness of cell movement. Resulting distributions show various segregation patterns of cell types. The condition for cell sorting is obtained from stability analysis of the set of diffusion equations governing the evolution of cell type distribution and the concentration of chemoattractant. The intensities of differential chemotaxis and random cell movement are quantitatively evaluated from experimental data to show that two cell types can sort themselves completely by these forces.

Heterogeneity in the circulating neutrophil pool: studies on subpopulations separated by continuous flow electrophoresis.

Isolated blood neutrophils from healthy individuals have been separated by continuous flow electrophoresis (CFE) as a Gaussian-shaped profile extending over 12-15 fractions, on the basis of differences in cell surface electrical charge. The fractions were pooled into three or four subpopulations; the mean electrophoretic mobilities of the least and most electronegative cells were 0.96 and 1.22 microns/sec/V/cm, respectively. Each pool of neutrophils was analyzed for functional and biochemical differences. Expression of respiratory burst in terms of the rate of superoxide production by the least and most electronegative cells to fixed concentrations of N-formyl-methionyl-leucyl-phenylalanine (fMLP, 10(-7) M) or phorbol myristate acetate (PMA, 1 microgram/ml) revealed that the least electronegative cells generated superoxide anion (O2-) at approximately twice the rate of the most electronegative cells. However, when lower concentrations of fMLP were used (1-5 x 10(-9) M), the most electronegative cells were most active. The least electronegative cells were also the most active in terms of phagocytosis and chemotaxis. In accordance with these differences in motile function, the basal F-actin content of the least electronegative cell pool was greater than the F-actin levels found in the most electronegative cells and remained so upon stimulation with fMLP. Such neutrophil heterogeneity as detected by CFE may be important in selective margination and recruitment of cells to inflammatory foci and sites of infection and may in part represent subsets of cells within the circulation that are primed in vivo to respond to inflammatory stimuli.

Phagocyte function in juvenile periodontitis

We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear.

Interrelation between taxis and sporulation systems

There are several hypotheses concerning the mechanism initiating sporulation and germination in bacteria. Here an account of current knowledge on the subject is given and a hypothesis is suggested, according to which chemotaxis and initiation of both sporulation and germination are governed by a common system. Chemotaxis and sporulation are two distinct behavioral systems of the Baciflus genera. Chemotaxis directs migration of cells to a favorable environment or away from harmful substances. Sporulation as a behavioral system is initiated in response to a deterioration of the external conditions and allows bacteria to survive during the unfavorable period. In the terms of chemotaxis, sporulation is a response to an increase in repellent concentrations or a decrease in attractant concentrations. The set of chemoeffectors for taxis and sporulation are very similar, the most common being amino acids and sugars. I suggest that the information concerning the outer medium (changes in chemoeffector concentrations) which is sensed by specific receptors, summed up and processed by the taxis system is transmitted not only to flagella, but to the sporulation system as well. Ordinarily, only the taxis system operates, but a certain critical increase in repellent concentration (or a decrease in attractant concentration) would trigger the sporulation system; accordingly, increase in attractant concentration would initiate germination. In analyzing the interrelationship between taxis and sporulation, we shall consider data obtained not only for Bacillus subtilis chemotaxis but also in studies of Escherichia coli chemotaxis, supposing that the mechanism of chemotaxis is basically similar in different bacterial species. Indeed, the main steps of information processing during taxis: reception, methylation of MCP proteins (methylaccepting chemotaxis proteins), Ca2+-regulated flagellar reversals were found to be alike in all major bacterial genera [3,14,28,30,35].