• YAKHAK HOEJI
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• v.52 no.5
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• 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.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.78-79
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• 2003

T cell activation is initited by the interaction of T cells with antigen-presenting cells (APCs) in the context of peptide antigen. Initial conjugates are formed by binding between lymphocyte-associated antigen-l (LFA-l, also known as CD11a-CD18) and intercellular adhesion molecule-l (ICAM-1), or CD2 and LFA-3, or other pairs of interactive proteins. (omitted)

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.100-112
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• 2001

Objective : The purpose of this study is to investigate the immunological effect of Ramulus Cinnamomum aqua-acupuncture on the cellular immune response in mice with LPS induced arthritis. Methods : All the BALB/C mice used in this study were bred and maintaned in our pathogen-free mouse colony and were 6wk of age at the start of the experiment. The experimental model of arthritis was induced by injeciton of 300${\mu}g$/kg LPS in mice knee joint. Ramulus Cinnamomum aqua-acupuncture was injected into Yangnungchon(Gb34) of mice 2daily for 14days. Immunohistochemical analysis was carried out to assess CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 expression in common iliac lymph nodes and synovial menbrane after stimulation with Ramulus Cinnamomum. Electron microscopy was carried out to assess change of synovial membrane. Ramulus Cinnamomum aqua-acupuncture stimulation group was compared to control group and non stimutated with aqua-acupuncture. Resutts : At day 14 post arthritis onset, Immunohistological studies using monoclonal antibodies showed that Ramulus Cinnamomum aqua-acupuncture goup had decreased expression of CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 at common illiac lymph nodes and synovial membrane compared with control group. Conclusions : Ramulus Cinnamomum aqua-acupuncture stimulation inhibited the development of cellular immunity to LPS-induced arthritis in mice. Thus, aqua-acupuncture stimulation may have preventive effects on autoimmune inflammatory joint diseases. The effects of AA on immune function and disease activity in patients with RA warrant further investigation.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.210-220
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• 1996

Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.936-944
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• 1996

Background: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. Adhesion molecules and gene transcription of the inflammatory mediators are known to be associated in this process. To evaluate whether adhesion molecule and transcriptional activation of the inflammatory substances are also involved in the activation of human alveolar macrophage by the adherence procedure, we designed this experiment. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be nonnal by chest cr and alveolar macrophage was harvested. To measure the expression of Interleukin-8(IL-8) mRNA, manganese superoxide dismutase(SOD) mRNA and CD11/CD18 mRNA in human alveolar macrophage of both adherence state and suspension state, Northern blot analysis was done at 0, 2, 4, 8 and 24hrs after the adherence to plastic surface and during suspension state. Then, phorbol myristate acetate(pMA) and N-formyl-methionyl-leucyl-phenylalanine(fMLP) were added respectively in the same experimental condition. Result : 1) Human alveolar macrophages in the adherent state induced IL-8 mRNA and SOD mRNA expression which was maximal at 8 hours after the adherence to plastic surface. But we could not observe the upregulation of CD18 mRNA by surface adherence. 2) PMA induced these mRNA expression both in the adherent cell and the nonadherem cells, but the induction of mRNA expression by fMLP occurred only in the adherent cells. Conclusion: These results suggest that adherence of huamn alveolar macropahge is an important cell-activating event that may play a critical role in the modulation of lung inflammatory respones.

• Journal of Periodontal and Implant Science
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• v.29 no.2
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• pp.333-350
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• 1999

The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.569-583
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• 1995

Background: The expression of the adhesion molecules on the cell surface is important in the movement of cells and the modulation of immune response. DILD starts as an alveolitis and progresses to pulmonary fibrosis. So adhesion molecules in these patients is expected to be increased. There are several reports about adhesion molecules in DILD in terms of the percentage of positive cells in immuno-stain, in which the interpretation is subjective and the data were variable. Methods: So we measured the relative median fluorescence intensity(RMFI) which is the ratio of the FI emitted by bound primary monoclonal antibody to FI emitted by isotypic control antibody of the cells in BALF of 28 patients with DILD(IPF:10, collagen disease:7, sarcoidosis:9, hypersensitivity pneumonitis:2) and 9 healthy control. Results: RMFI of the ICAM-1 on AM($3.30{\pm}1.16$) and lymphocyte($5.39{\pm}.70$) of DILD were increased significantly than normal control($0.93{\pm}0.18$, $1.06{\pm}0.21$, respectively, p=0.001, P=0.003). RMFI of the CD18 on lymphocyte was also higher($24.9{\pm}14.9$) than normal($4.59{\pm}3.77$, p=0.0023). And there was a correlation between RMFI of ICAM on AM and the % of AM(r=-0.66, p=0.0001) and lymphocyte(r=0.447, p=0.0116) in BALF. Also RMFI of ICAM on lymphocyte had a significant (r=0.593, p=0.075) correlation with the % of IL-2R(+) lymphocyte in BALF. The soluble ICAM(sICAM) in serum was also significantly elevated in DILD($499.7{\pm}222.2\;ng/ml$) compred to normal($199.0{\pm}38.9$) (p=0.00097) and sICAM in BAL fluid was also significantly higher than normal control group($41.8{\pm}23.0\;ng/ml$ vs $20.1{\pm}13.6\;ng/ml$). There was a Significant correlation between sICAM level in serum and the expression of ICAM-l on AM(r=0.554, p=0.0259).Conclusion: These data suggest that in DILD the expression of adhesion molecules is increased in the AM and BAL lymphocytes with elevated serum sICAM, and these parameter may be useful in determining disease activity.