• BMB Reports
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• v.49 no.9
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• pp.520-525
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• 2016

We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector-expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken together, our results suggest that the two AMPs stimulate neutrophils, leading to chemotactic migration through FPR1, and the two AMPs will be useful for the study of FPR1 signaling and neutrophil activation.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.137-143
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• 1994

Enhancement or diminution of leukocyte migration to the specific site might be important factors for the development of inflammatory diseases. To investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on chemotaxis of neutrophil, we obtained neutrophils by Hypaque-Ficoll step gradient centrifugation and tested the effects of seven drugs on the n-formyl-leucyl-phenylalanine (FMLP)-induced migration of neutrophil using a 48-well micro chemotaxis assembly. Oxyphenbutazone, phenylbutazone, sulindac, zomepirac, and ibuprofen suppressed the migration of neutrophil at the therapeutic concentrations, however, indomethacin showed stimulation effect. IC50s for inhibition of neutrophil migration by these drugs are less than 100uM. When drugs were preincubated with FMLP, no inhibition on migration of neutrophil was observed. These results indicated that inhibitory effects of these drugs on migration of neutrophil might be related to the receptor sites of neutrophil rather than molecular inactivation of chemoattractant (FMLP). In conclusion, we suggested that the property of inhibition effects on neutrophil migration of several NSAIDs might be another mode of pharmacological action for anti-iflammatory effect, which showed significant effects at concentrations below therapeutic levels, in addition to cyclooxygenase inhibition.

• Korean Journal of Veterinary Research
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• v.31 no.3
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• pp.285-294
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• 1991

In this study, the immunomodulating effects of levamisole, selenium and tocopherol on blood neutrophils and peritoneal macrophages of goat were evaluated in vitro and in vivo. The functions of blood neutrophils and peritoneal macrophages were assayed by random and direct migration, phagocytosis of S aureus, production of superoxide and hydrogen peroxide. The results obtained were summarized as follows: In vitro trials 1. Levamisole treatment enhanced the random and direct migration of goat blood neutrophils when compared with untreated cell, and a significant (p<0.01) enhancement was noticed at the concentration of $100{\mu}g$ for direct migration and $50{\mu}g{\sim}1,000{\mu}g\;per\;ml$ of culture medium for random migration. There was no influence of selenium and tocopherol on random and direct migration of neutrophil at all of treatment concentration. 2. Neutrophils produced higher levels of superoxide by lcvamisole treatment at the concentration of $100{\mu}g$ and by selenium treatment at the concentration of $1.0{\mu}g$, but the production of hydrogen peroxide was not increased. Tocopherol had no effect on the production of antimicrobicidal oxygen metabolites of neutrophils at various concentrations. 3. No differences of phagocytic activity were observed when neutrophils were treated with three substances. In vivo trials 1. Blood neutrophils of goats orally administered levaraisole showed significantly (p<0.05) higher random migration from 2 to 24 hours after feeding (2.5mg/kg of body weight). Augmentation of random migration of neutrophil from goats orally administered selenium-tocopherol mixture (selenium $100{\mu}g$-tocopherol 200IU/head/day) was observed at 10 days and the significant (p<0.05) increase was shown from 30 days after feeding and continued throughout the feeding periods. 2. There was no effect on phagocytic activity and production of antimicrobicidal oxygen metabolites of neutrophils from goats administered levamisole or selenium-tocopherol mixture. 3. Random migration, production of superoxide and hydrogen peroxide and S aureus phagocytic activity of peritoneal macrophages of goats administered 300ml of levamisole-thioglycollatc medium mixture $(2.5{\mu}g/ml)$ into peritoneal cavity increased significantly (p<0.01 or p<0.05) when compared with those of goats administered thioglycollate medium alone.

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1638-1642
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• 2008

Cell migration is one of the essential mechanisms responsible for complex biological processes. Intensive researches have begun to elucidate the mechanisms and search intriguing conditions for efficient control of cell migration. One general mechanism which is widely applicable for cells including neutrophil, Escherichia coli and endothelial cell is chemotaxis. Especially, understanding the chemotactic mechanics of cell crawling has important implications for various medical and biological applications. The single cell study for chemotaxis has an advantage over studies with the population of cells in providing a clearer observation of cell migration, which leads to more accurate assessments of chemotaxis. In this paper, we propose a three-dimensional model considering a single crawling cell to study its chemotaxis. The semi-implicit Fourier spectral method is applied for high efficiency and numerical stability. The simulation results reveal rich dynamics of cell.

• Biomedical Science Letters
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• v.20 no.3
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• pp.111-116
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• 2014

Human neutrophils play an essential role in the innate immune response and are involved in the pathogenesis of the severe and corticosteroid-resistant asthma. Asthma is characterized by an infiltration of inflammatory cells into the lung and by a cytokine release. The aim of this study is to investigate the effects of a bronchoalveolar lavage fluid (BALF) on the chemotaxis and apoptosis of neutrophils which were isolated from healthy subjects. The BALF of subjects with asthma induces the blood neutrophil chemotaxis in the opposite of that in normal subjects. The IL-8, IL-6, and monocyte chemoattractant protein-1 (MCP-1) levels in BALF were higher in subjects with asthma than in normal subjects. The BALF of normal and asthmatic subjects has no effect on neutrophil apoptosis of BALF. MCP-1 delays the constitutive apoptosis of normal blood neutrophils, but has no effect in normal BALF neutrophils. These results may indicate that inflammatory factors secreted by the lung tissue of patients with asthma trigger the neutrophil chemotaxis and also induce the neutrophil dysregulation.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.579-589
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• 1996

Background : Activation of neutrophil is critical for the clearance of microorganisms and toxic host mediators during sepsis. Unfortunately the activated neutrophil and its toxic byproducts can produce tissue injury and organ dysfunction. The leucocyte CD11/18 adhesion complex regulates neutrophil-endothelial cell adhesion, the first step in neutrophil migration to sites of injection and inflammation. To investigate the potential of neutrophil inhibition as a treatment strategy for sepsis, we evaluated the effects of monoclonal antibody against CD11b (MAb 1B6) in rats intrabronchial challenged with Escherichia coli. Methods : Animals were randomly assigned to receive monoclonal antibody against CD11b (1 mg/kg, sc) and bovine serum albumin(BSA, 1 mg/kg, sc) 6 hr before, at 0 and 6 hr after intrabronchial challenge of $20x10^9$ CFU/kg E. coli 0111. Animals were randomized to treat either 24, 60 or 90% oxygen after bacterial challenge and begining 4 hr after inoculation, all animals were received 100 mg/kg ceftriaxone qd for 3 days. Peripheral and alveolar neutrophil(by bronchoalveolar lavage) counts and lung injury parameters such as alveolar-arte rial $PO_2$ difference, wet to dry lung weight ratio and protein concentration of alveolar fluid were measured in survived rats at 12 hr and 96 hr. Results : Monoclonal antibody against CD11b decreased circulating and alveolar neutrophil especially more in 12 hr than in 96 hr The lung injury parameters of antibody-treated animals were not different from those of BSA-treated animals. but It was meaningless due to small number of survived animals. The early(6 hr) mortality rate was significantly increased in antibody-treated group(51%) compared to BSA-treated group(31%) (P=0.02) but late(from 12 hr to 72 hr) mortality rate was not different in antibody-treated group(44%) from BSA-treated group(36%) (P =0.089). Conclusion : Leucocyte CD11b/18 adhesion molecule is known to regulate neutrophil migration to the site of infection and inflammation. The monoclonal antibody against CD11b decreased alveolar neutrophil in rats with pulmonary sepsis and increased early mortality rate. Therefore, we can speculate that monoclonal antibody against CD11b blocks of alveolar recruitment of neutrophils, impairs host defense mechanism and increases early mortality rate of pulmonary sepsis in rat.

• Journal of Periodontal and Implant Science
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• v.54 no.2
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• pp.85-95
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• 2024

Purpose: Developmental endothelial locus-1 (DEL-1) plays a role in regulating neutrophil migration within the periodontium. The objective of this study was to evaluate the levels of DEL-1 in saliva and gingival crevicular fluid (GCF), as well as the number of neutrophils in patients with periodontitis. Methods: Forty systemically healthy, non-smoking periodontitis patients participated in this study. Clinical periodontal parameters, including the plaque index, probing pocket depth (PPD), clinical attachment level, bleeding on probing, modified sulcular bleeding index, and marginal bone level, were measured. Levels of DEL-1, interleukin (IL)-1β, IL-6, and IL-8 in unstimulated saliva samples, as well as DEL-1 in the GCF of 3 teeth from each participant, were assessed. Neutrophil counts in oral rinse and GCF samples were recorded. Spearman correlation coefficients were used to examine the correlation between protein levels, clinical parameters, and neutrophil quantities. Participants were divided into 2 age groups (those under 50 years and those 50 years or older) in order to investigate potential age-related differences. Results: DEL-1 levels in the GCF showed a negative relationship with PPD (sum). Neutrophils in oral rinse samples were positively correlated with PPD, IL-8, and IL-1β levels. Neutrophils in GCF exhibited a positive correlation with PPD (sum). Salivary DEL-1 levels showed correlations with IL-8 and IL-1β, but not with the clinical parameters of periodontitis. Conclusions: The negative relationship observed between PPD and GCF DEL-1 levels is consistent with the proposed protective role of DEL-1.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.103-106
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• 2003

The epithelial cells that form a barrier lining the lung airway are key regulators of neutrophil trafficking into the airway lumen in a variety of lung inflammatory diseases. Although the lipid mediator leukotriene B$_4$ (LTB$_4$) is known to be a principal chemoattractant for recruiting neutrophils to inflamed sites across the airway epithelium, the precise signaling mechanism involved remains largely unknown. (omitted)

• Interaction and multiscale mechanics
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• v.4 no.2
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• pp.165-171
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• 2011

In this study, we proposed a three-dimensional dynamic model under the diffuse interface description for the single crawling cell. From the developed model, we described the clear evolution processes for crawling neutrophil and assessed the reliable quantitative chemotactic property, which confirmed the high possibility of adequate predictions. To establish the system considering of multiple mechanisms such as, diffusion, chemotaxis, and interaction with surface, a diffuse interface model is employed.

• Biomedical Science Letters
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• v.12 no.3
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• pp.145-151
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• 2006

Leukotactin-l (Lkn-l )/CCL15 has been known as a potent chemoattractant of leukocytes. However, the precise function of Lkn-l in human neutrophils has not been explained well. In the present study, we investigated the contribution of Lkn-1 in chemotactic activity of human neutrophils. Both CCR1 and CCR3 mRNA expressions are strongly expressed in human neutrophils but CCR2 protein expression was uniquely detected on the cell surface. Lkn-l binding to CCR1 and CCR3 induced chemotactic activity of neutrophils. Chemotactic index of Lkn-l was comparable to that of IL-8. $MIP-1{\alpha}/CCL3$ binding to CCR1 and CCR5 has no effect on neutrophil migration. Cell migration, in response to Lkn-l, was blocked by pertussis toxin (Ptx), a $G_o/G_i$ protein inhibitor, and U73122, a phospholipase C(PLC) inhibitor but not by protein kinase C inhibitor such as rottlerin, and Ro-31-8425. Taken together, our results demonstrate that Lkn-l transduces the chemotaxis signal through $G_o/G_i$ protein and PLC. This finding provides the molecular mechanism by which Lkn-l may contribute to neutrophil movement into the site of inflammation.