Sepsis remains one of the leading causes of death globally, in spite of advanced developments in intensive care and better understandings of pathophysiology related to sepsis. There is no special treatment or drug available for sepsis, currently. Under normal circumstances, neutrophil is a major player in acute infection control. However, during sepsis, the migration abilities and antimicrobial functions of neutrophils are impaired, resulting in a dysregulated immune response. Recent studies have indeed demonstrated that blocking or reversing neutrophil migration and impaired antibacterial function can improve the outcomes in septic animal models. This article systemically synthesized information regarding related factors and signaling involved in the functions of neutrophils in sepsis. This review also discussed the possibility that neutrophils be used as a marker for specific diagnosis and/or prediction of the outcomes of sepsis.
Animals ; Neutrophils/physiology* ; Chemotaxis ; Chemotaxis, Leukocyte ; Sepsis ; Cell Movement

Reduced chemotactic migration of polymorphonuclear neutrophil (PMN) in sepsis patients leads to decreased bacterial clearance and accelerates the progression of sepsis disease. Quantification of PMN chemotaxis in sepsis patients can help characterize the immune health of sepsis patients. Microfluidic microarrays have been widely used for cell chemotaxis analysis because of the advantages of low reagent consumption, near-physiological environment, and visualization of the migration process. Currently, the study of PMN chemotaxis using microfluidic chips is mainly limited by the cumbersome cell separation operation and low throughput of microfluidic chips. In this paper, we first designed an inertial cell sorting chip to achieve label-free separation of the two major cell types by using the basic principle that leukocytes (mainly granulocytes, lymphocytes and monocytes) and erythrocytes move to different positions of the spiral microchannel when they move in the spiral microchannel under different strength of inertial force and Dean's resistance. Subsequently, in this paper, we designed a multi-channel cell migration chip and constructed a microfluidic PMN inertial label-free sorting and chemotaxis analysis platform. The inertial cell sorting chip separates leukocyte populations and then injects them into the multi-channel cell migration chip, which can complete the chemotaxis test of PMN to chemotactic peptide (fMLP) within 15 min. The remaining cells, such as monocytes with slow motility and lymphocytes that require pre-activation with proliferative culture, do not undergo significant chemotactic migration. The test results of sepsis patients ( n=6) and healthy volunteers ( n=3) recruited in this study showed that the chemotaxis index (CI) and migration velocity ( v) of PMN from sepsis patients were significantly weaker than those from healthy volunteers. In conclusion, the microfluidic PMN inertial label-free sorting and chemotaxis analysis platform constructed in this paper can be used as a new tool for cell label-free sorting and migration studies.
Humans ; Chemotaxis ; Neutrophils/metabolism* ; Microfluidics ; Cell Movement ; Sepsis/metabolism*

Improved approaches for promoting umbilical cord blood (CB) hematopoietic stem cell (HSC) homing are clinically important to enhance engraftment of CB-HSCs. Clinical transplantation of CB-HSCs is used to treat a wide range of disorders. However, an improved understanding of HSC chemotaxis is needed for facilitation of the engraftment process. We found that ectopic overexpression of miR-9 and antisense-miR-9 respectively down- and up-regulated C-X-C chemokine receptor type 4 (CXCR4) expression in CB-CD34⁺ cells as well as in 293T and TF-1 cell lines. Since CXCR4 is a specific receptor for the stromal cell derived factor-1 (SDF-1) chemotactic factor, we investigated whether sense miR-9 and antisense miR-9 influenced CXCR4-mediated chemotactic mobility of primary CB CD34⁺ cells and TF-1 cells. Ectopic overexpression of sense miR-9 and antisense miR-9 respectively down- and up-regulated SDF-1-mediated chemotactic cell mobility. To our knowledge, this study is the first to report that miR-9 may play a role in regulating CXCR4 expression and SDF-1-mediated chemotactic activity of CB CD34⁺ cells.
Cell Line ; Cell Movement ; Chemotaxis ; Fetal Blood ; Hematopoietic Stem Cells ; MicroRNAs ; Stromal Cells

Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L ^-1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L ^-1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Cell Movement ; Chemotaxis ; Equipment Design ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Microfluidics ; Neutrophils ; Reproducibility of Results

The investigation of the mechanism of biological pattern has been an important topic of life sciences, especially, of developmental biology, for a long time. It is an interdisciplinary problem and many researching data have been obtained and some theories have been structured from many points of view in science. However, up to now, the actual mechanism is still a fascinating puzzle and needs more studies. In this paper, we try to construct a cellular automata model of biological pattern. This model defines the individual model cells and their behaviors, cell-cell interactions, and cell-environment interactions. As an application, we present a new discrete model to simulate the aggregation phase of the development of Dictyostelium discoideum with the concept of "inducing switch".
Animals ; Cell Aggregation ; physiology ; Cell Movement ; physiology ; Dictyostelium ; cytology ; physiology ; Models, Biological

OBJECTIVETo study the effects of very late antigen(VLA) antagonist BIO-1211 on eosinophil chemotaxis, recruitment and mediator release.

METHODSEosinophil chemotaxis was induced by platelet activating factor(PAF) in vitro and eosinophil recruitment and release were determined in vivo.

RESULTVLA antagonist BIO-1211 inhibited eosinophil chemotaxis induced by PAF. The inhibitory rates at 4x10(-11), 4x10(-10), 4x10(-9) mol x L(-1) were 24.9%, 29.9%, and 31.3%, respectively. Pretreatment by BIO-1211 1, 3 and 10 mg x kg(-1) intraperitoneally inhibited the recruitment of eosinophils in PAF in the rat induced by Sephadex in a dose dependent manner. Inhibitory rates were 60.3%, 68.9%, and 72.9%(P<0.05), respectively. BIO-1211 did not inhibit eosinophil peroxidase(EPO) release from eosinophils.

CONCLUSIONBIO-1211 inhibits eosinophil chemotaxis and recruitment, alleviates local inflammation, and may represent a new type of drug for allergic diseases.

Animals ; Cell Movement ; drug effects ; Chemotaxis, Leukocyte ; drug effects ; Dose-Response Relationship, Drug ; Eosinophil Peroxidase ; Eosinophils ; drug effects ; physiology ; Integrin alpha4beta1 ; antagonists & inhibitors ; physiology ; Male ; Oligopeptides ; pharmacology ; Peroxidases ; secretion ; Platelet Activating Factor ; pharmacology ; Rats ; Rats, Sprague-Dawley

In order to evaluate antitumor rnechanisms of interleukin (IL)-12/IL-2 that has been shown significant tumor suppressive activity on established primary and metastatic Renca tumor, we studied chemokine gene expression induced by direct action of IL- 12/IL-2 or cytokine cascade. IL-12/IL-2 induced gene expression of interferon gamma (IFN-r) and granulocyte monocyte-colony stimulating factor (GM-CSF) in splenocytes, and it induced gene expression of monokine induced by IFN-r (Mig), interferon inducible protein 10 (IP- 10), SDF-1, macrophage inflammatory protein (MIP)-1a, MIP-1B, MIP-2, monocyte chemotactic protein (MCP)-1, and Rantes in tumor mass. However IL-12/IL-2 could not induce these chemokines in tumor mass of GKO mice and Renca cell in vitro. IL- 12 also did not increased chemokine gene expression in Renca cell in vitro, but IFN-r induced gene expression of Mig, IP-10, MCP-1 in Renca cell in vitro. In the chemotaxis assay, culture supernatant of Renca cell stimulated with IFN-r increased splenocyte migration in vitro. All these data suggest IL-12/IL-2 can induce IFN-r-chemokine cascade in tumor mass, and Mig, IP-10, MCP-1 produced from tumor cell may play an important role for initial immune cell migration into tumor mass.
Animals ; Cell Movement ; Chemokine CCL5 ; Chemokine CXCL10 ; Chemokines ; Chemotaxis ; Gene Expression* ; Granulocytes ; Interferons ; Interleukins ; Macrophages ; Mice ; Monocytes

OBJECTIVE: To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system. METHODS: In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis. RESULTS: The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×10⁴/mL,(0.05±0.02)×10⁴/mL,(0.32±0.01)×10⁴/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) μm/s,(0.12±0.01) μm/s,(0.14±0.01) μm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) μm,(134.61±0.01) μm,(156.19±0.01) μm respectively(P<0.05). CONCLUSION Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.
Animals ; Cell Movement ; Chemokines ; Chemotaxis ; Disease Models, Animal ; Dizocilpine Maleate ; Mice ; Neutrophils/physiology* ; Peritoneal Cavity ; Rats ; Schizophrenia/physiopathology*

OBJECTIVETo isolate and culture mesenchymal stem cells ( MSC) from different sources and to investigate the chemotactic effects of burn rat serum on MSC derived from different sources.

METHODSSeventy-two Wistar rats were randomly divided into burn( n = 36, with 30% TBSA full-thickness burns on the back) and sham burn (n = 36, without burns) groups. Bone marrow and peripheral blood of the rats in both groups were collected to isolate and culture MSC. Ratio of MSC, growth speed and cell morphology were observed with inverted microscope. Effects of different serum ( fetal bovine serum, normal rat serum and burn rat serum) on chemotaxis of MSC derived from different sources and their migration ability were subsequently examined with a transwell system. Results MSC were obtained from bone marrow of the rats in both groups. MSC were successfully obtained from bone marrow of all burn rats(100% , P <0.05) , but only from peripheral blood of 7 burn rat(58% ) , and no MSCs were obtained from peripheral blood of 12 rats in sham group( P <0.05). There was small amount of adherent cells 24 hrs after culture, and fusiform shaped adherent cells were sporadically observed in scattered distribution 2-3 days later with inverted microscope. There was no obvious difference in the cell morphology between the 2 groups. In the sham group, the number of MSC migrating to the lower surface of transwell after burn serum treatment [ (94 Il ) cells/ high power field] was significantly greater than that after the treatment with normal rat serum and fetal bovine serum [ (37 +/- 6) , (38 +/- 11) cells/high power field , P <0.01 ] , while no difference in migration ability was found after normal serum treatment compared with that after fetal bovine serum treatment ( P >0. 05). The migration rate of MSCs which were derived from bone marrow in sham group was obviously lower than those derived from bone marrow and peripheral blood from burn rats ( P <0. 05 or 0. 01). Though some difference of the migration ability existed between MSC derived from bone marrow and peripheral blood, there was no statistically significant difference ( P >0. 05).

CONCLUSIONMSC can be isolated and cultured from bone marrow and peripheral blood of burn rat, but not from peripheral blood of normal rat. Burn rat serum has a stronger chemotactic effect on MSC. Moreover, the migration ability of MSC derived from burn rat is stronger than that of MSC derived from normal rat.

Animals ; Bone Marrow Cells ; cytology ; Burns ; blood ; Cell Differentiation ; Cell Movement ; Cell Separation ; Cells, Cultured ; Chemotaxis ; Disease Models, Animal ; Male ; Mesenchymal Stromal Cells ; cytology ; Rats ; Rats, Wistar ; Serum

OBJECTIVETo investigate the expression of chemokine receptor CXCR4 and its ligand CXCL12 in oral squamous cell carcinoma (OSCC) cells, and their effects on proliferation and migration of tumor cells.

METHODSThe expression of CXCR4 mRNA and protein in 20 cases of OSCC tissue, cervical lymph nodes, tongue cancer cell line Tca8113, buccal cancer cell line Bca885, and 10 specimens of normal oral mucosa tissue were examined by reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blot. The expression of CXCL12 mRNA was examined by RT-PCR. MTT assay was used to evaluate the CXCR4/CXCL12 influence on proliferation of tumor cells. Chemotaxis and migration response to CXCR4 particular ligand-CXCL12 were detected by chemotaxis assay.

RESULTS1) Expression levels of CXCR4 mRNA and protein in OSCC tissues, Tca8113 and Bca885 cells were 2.31 +/- 1.13, 1.89 +/- 1.20, 1.67 +/- 1.10 and 1.36 +/- 0.15, 1.85 +/- 0.34, 1.97 +/- 0.23, respectively. CXCR4 mRNA and protein couldn't be detected in normal tissues. CXCL12 mRNA level in cervical lymph nodes was 1.14 +/- 0.87, CXCL12 mRNA couldn't be detected in OSCC and normal tissues. 2) In MTT assay, recombinant CXCL12 stimulated proliferation of tumor cells and CXCR4 neutralization by monoclonal antibodies decreased proliferation. 3) The chemotactic migration of OSCC cells could be induced by CXCL12. CXCL12 at a concentration between 30 ng x mL(-1) and 100 ng x mL(-1) induced the chemotactic migration of OSCC cells in a dose-dependent manner.

CONCLUSIONCXCR4/CXCL12 system may promote proliferation and migration of tumor cells, and may play an important role in lymph node metastasis of OSCC.

Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Movement ; Chemokine CXCL12 ; Chemotaxis ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Mouth Neoplasms ; RNA, Messenger ; Receptors, CXCR4