• Journal of Life Science
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• v.34 no.1
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• pp.48-58
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• 2024

Salmonella is a common food-borne intracellular bacterial pathogen that has triggered significant public health concerns. Salmonella hosts' genetic factors play a pivotal role in determining their susceptibility to the pathogen. Cysteine-rich intestinal protein 1 (CRIP1), a member of LIM/double zinc finger protein family, is widely expressed in humans, such as in the lungs, spleen, and especially the gut. Recently, CRIP1 has been reported as a key marker of several immune disorders; however, the effect of CRIP1 on bacterial infection remains unknown. We aimed to elucidate the relationship between Salmonella infection and CRIP1 gene deficiency, as Salmonella spp. is known to invade the Peyer's patches of the small intestine, where CRIP1 is highly expressed. We found that CRIP1-deficient conditions could not alter the characteristics of bone marrow-derived myeloid cells in terms of phagocytosis on macrophages and the activation of costimulatory molecules on dendritic cells using ex vivo differentiation. Moreover, flow cytometry data showed comparable levels of MHCII⁺CD11b⁺CD11c⁺ dendritic cells and MHCII⁺F4/80⁺CD11b⁺ macrophages between WT and CRIP1 knockout (KO) mice. Interestingly, the basal population of monocytes in the spleen and neutrophils in MLNs is more abundant in a steady state of CRIP1 KO mice than WT mice. Here, we demonstrated that the CRIP1 genetic factor plays dispensable roles in host susceptibility to Salmonella Typhimurium infections and the activation of myeloid cells. In addition, differential immune cell populations without antigen exposure in CRIP1 KO mice suggest that the regulation of CRIP1 expression may be a novel immunotherapeutic approach to various infectious diseases.

• Korean Journal of Transplantation
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• v.32 no.4
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• pp.108-112
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• 2018

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.

• Journal of Life Science
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• v.27 no.2
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• pp.217-224
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• 2017

Carbon monoxide (CO), a reaction product of cytoprotective enzyme heme oxygenase-1 (HO-1), is a gaseous messenger with anti-proliferative, anti-apoptotic, and anti-inflammatory actions in many cell types. Here, we investigated the role of CO on the process of monocyte differentiation induced by phorbol 12-myristate 13-acetate (PMA) in human monocytic THP-1 cells. CORM-2 (tricarbonyldichlororuthenium (II) dimer, $Ru2Cl_4(CO)_6$), a CO-releasing compound, decreased a marked cell adherence with a slight reduction of proliferation in monocytic THP-1 cells treated with PMA. And, CORM-2 significantly inhibited expression of differentiation markers such as CD14, CD11b plus CD18 (macrophage-1 antigen, Mac-1 or complement receptor 3, CR3) and phagocytosis of carboxylate-modified red fluorescent latex beads, in PMA-stimulated THP-1 cells. For the further experiments, differentiation of PMA-treated cells was enhanced after the initial 2 days stimulus by removing the PMA-containing media then incubating the cells in fresh media for a another 4 days. And, we observed the secretion of inflammatory cytokines and phagocytosis in differentiated macrophages. Treatment with CORM-2 significantly abolished the secretion of IL-6, $TNF-{\alpha}$ and phagocytosis using fluorescence-conjugated E. coli (K-12 strain) bioparticles in lipopolysaccharide (LPS)-stimulated differentiated macrophages. In conclusion, these results suggest that CO inhibits the differentiation of monocytic THP-1 cells as well as the activation of differentiated macrophages.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.779-788
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• 2005

Purpose : Echinacea, a traditional plant medicine has been used as immune-stimulant. Recent studies have revealed that extract of Echinacea has immunostimulatory effects on human blood mononuclear cells. This study was designed for the purpose of screening the genes associated with immunologic effects of Echinacea on monocytes and dendritic cells using a cDNA microarray chip. Methods : $CD14^+$ monocyte cells were cultured for one day with Echinacea extract(final concentration : $50{\mu}g/mL$) in experiment 1, but were cultured without Echinacea in experiment 2. The gene expression of these cultured monocytes was analyzed using the cDNA microarray chip. Dendritic cells produced from $CD14^+$ monocyte were cultured for five days with GM-CSF and IL-4, and then cultured for one day with Echinacea in experiment 3, but were done without Echinacea in experiment 4. Results : In experiments 1 and 2, there were 17 significantly expressed genes with average expression ratios above 2.5, including interferon gamma-inducible protein 30(IFI 30), CDC(cell-division-cylcle)-like kinase 2(CLK 2), syndecan binding protein(syntenin), superoxide dismutase 2, etc. In experiments 3 and 4, there were 24 gene, with significantly expressed genes were 24 genes, which were insulin-like growth factor 2(somatomedin A), methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A, member 22, etc. The genes encoding CD44, IFI 30, mannose receptor C type 1(MRC 1), chemokine receptor 7(CCR 7), CLK 2, syntenin and cytochrome C oxidase subunit VIII were significantly expressed in both monocytes and dendritic cells cultured with Echinacea. Conclusion : This study employed a cDNA microarray chip to elicit the immune-associated gene profile; the expression was enhanced by Echinacea in CD14+ monocytes and dendritic cells. Thus we laid the basis for the quantitative and functional analysis of genes induced by Echinacea in monocytes and monocyte-derived dendritic cells.

• Korean Journal of Veterinary Research
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• v.41 no.2
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• pp.211-218
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• 2001

The $M_r$ 63,000 glycoprotein (GP63) and lipophosphoglycan (LPG) of Leishmania donovani were evaluated as vaccine candidates against visceral leishmaniasis. Mice were immunized with liposomeencapsulated GP63 and/or LPG that were purified from the soluble extract of L. donovani promastigotes, and were challenged with virulent amastigotes. Mice immunized with GP63/LPG in liposomes plus BCG resulted in a 27.4% reduction of amastigotes in the liver compared to the control group (liposomes plus BCG), and mice immunized with liposome-GP63 plus BCG failed to induce a protective immune response against the challenge infection. Immunization of mice with GP63 fused to the Schistosoma japonicum glutathione S-transferase (GP63-GST) plus BCG also failed to elicit protective immunity. To analyze the cause of failure to induce protection, cytokine release from the spleen cells of immunized mice and Leishmania-specific serum antibodies were analyzed. Spleen cells from mice immunized with GP63-GST plus BCG that were exposed to soluble extract of L. donovani in vitro produced 10-fold greater quantities of IFN-gamma and 3-fold greater quantities of IL-5 than cells from mice receiving BCG only or saline. Western blot analysis revealed that sera from these mice had Leishmania-specific antibodies recognizing 1 to 3 antigens of L. donovani with M. W. of 60-65 kDa. Although immunization of mice with GP63-GST induced a strong Th1 response, this study indicated that GP63-GST simultaneously elicited the Th2 response of the CD4+ T-cell, which was known to abrogate the protective immune response conferred by the Th1 effector function.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.437-443
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• 2018

Activation of macrophages plays an important role in the host-immune system. In this study, we investigated the functional roles and related signaling mechanism of hot-water extracts of bee pollen (BPW) in RAW 264.7 macrophages. Since BPW did not exert cytotoxicity at concentrations ranging from 62.5 to $250{\mu}g/mL$ in macrophage cells, a concentration of $250{\mu}g/mL$ was used as the maximum dose of BPW throughout subsequent experiments. BPW increased inducible nitric oxide synthase-mediated nitric oxide production in a concentration-dependent manner. Additionally, BPW was found to induce macrophage activation by augmenting the expression of cell surface molecules (cluster of differentiation; CD80/86, and major histocompatibility complex; MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis $factor-{\alpha}$, interleukin-6, and $IL-1{\beta}$) through mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ signaling pathways in RAW 264.7 macrophages. Taken together, our results indicate that BPW could potentially be used as an immunomodulatory agent.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.182-190
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• 2015

This present study demonstrates the immunological synergistic effects of herbal preparation (HemoHIM) and red ginseng powder granule in various immune cell models (bone marrow-derived macrophages, dendritic cells, and mouse splenocytes) from mice. Both herbal preparation and red ginseng extracts were treated to bone-marrow derived macrophages, dendritic cells, and mouse splenocytes, and there was no cytotoxicity at a dose below $200{\mu}g/mL$. Cell proliferation and cytokine [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-12] production tested in bone marrow-derived macrophages and dendritic cells significantly increased upon combined treatment. Cell surface marker (CD 80/86, MHC class I/II)-mediated immune cell activation was highly elevated by combined treatment. For cytokine production in splenocytes, combined treatment significantly increased production of Th 1 type cytokines [IL-2 and interferon (IFN)-${\gamma}$] but not Th 2 type cytokines (IL-4 and IL-10). Therefore, combined treatment with HemoHIM and red ginseng extracts is an effective method to establish powerful immunological synergy in immune cells.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.484-488
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• 1994

Background : The antigen-specific receptor on the surface of most peripheral T lymphocytes is a disulfide-linked heterodimer composed of $\alpha$ and $\gamma$ subunits, noncovalently associated with CD3 polypeptides. Recently, a novel type of CD3-associated heterodimer was described on a T cell subset that does not express CD4 or CD8 molecules. This second type of TCR dimer is composed of chains encoded for by the $\gamma$- and $\delta$-TCR genes. These cells may exert both cytotoxic and lymphokine producing functions. Although it was reported that some ${\gamma}{\delta}$-TCR might recognize an MHC-linked determinant, the funεtion or physiologic ligand for this new receptor is not yet clear. It was found that ${\gamma}{\delta}$-TCR can react with 65 kD heat shock protein of M. tuberculosis, which suggests the possible protective role of ${\gamma}{\delta}$ T lymphocytes against tuberculosis. In our previous study, there was neither the increase in number nor the functional activation of ${\gamma}{\delta}$ T cells in the peripheral blood from patients with pulmonary tuberculosis. Now we report the distribution of ${\gamma}{\delta}$ T cells in the regional sites of M. tuberculosis infection, especial1y tuberculous lymphadenitis. Methods : Lymph nodes from patients with pathologically-proven tuberculous lymphadenopathy (n=5) and reactive hyperplasia (n=3) were used. Tissues were frozen in liquid nitrogen immediately after removal and stored below $-70^{\circ}C$. The cryostat sections of these frozen specimens were stained with anti-Leu-4 Ab, Identi-T TCR ${\delta}1$, and Identi-T ${\beta}F1$. The number of positively stained cells were counted at high power field. Results : The infiltration of ${\gamma}{\delta}$ T cells was significantly higher in the lymph nodes from patients with tuberculous lymphadenopathy than that with reactive hyperplasia ($16.3{\pm}10.3%$ vs. $1.7{\pm}1.5%$). Conclusion : These results suggest that ${\gamma}{\delta}$) T cells may play a role in the defense against M. tuberculosis infection, especially in the regional sites of infection.

• Journal of Chest Surgery
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• v.40 no.3 s.272
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• pp.180-192
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• 2007

Background: As determined from the recent investigations of discordant cardiac xenotransplantation, hyperacute rejection occurs mainly at the endothelial cells in donor microvascular systems, but this does not occur at cardiac valve leaflets or at medium-to-large caliber vessels. On the basis of this background, this study was performed to look into the biocompatibility for transplantation of a middle or large diameter xenogenic blood vessel by conducting xenogenic arterial transplantation with the carotid artery in a pig-to-goat model. Material and Method: The experimental group was composed of 10 pairs of pig-to-goat combinations. They were divided into each period of 1 week, and 1, 3, 6 and 12 months. Four carotid artery grafts obtained through collection of the bilateral carotid arteries from two pigs were preserved at $-70^{\circ}C$ without other treatment, and then they were transplanted into the bilateral carotid arteries of two goats. Doppler ultrasonography was done on a periodic basis after transplantation to evaluate the patency of the grafted blood vessel. At the ends of a predetermined period, the grafts were explanted from the goats and they underwent gross examination. Hematoxylin-eosin and Masson's trichrome staining were conducted. In addition, in order to examine the immunological rejection of the grafted xenogenic blood vessel, immunohistochemical staining was conducted with T-lymphocyte indicator and von Willebrand factor. Result: Two goats at the each one-week period and the one-year period died during the experimental period because of a reason unrelated to the experimental procedure, and the remaining 8 goats survived until the end of each experiment period. On Doppler ultrasonography, unilateral carotid artery occlusion was found in a goat, whose period was specified as 3 months, among the 8 survived goats. However, the vascular patency was maintained well and there was no graft that formed aneurysms in the other goats. On gross examination, the region of vascular anastomosis was preserved well, and calcification of the grafted blood vessel was not shown. Histologically, the endothelial cells of the graft disappeared one week after transplantation, and then there was progressive spread of the recipients' endothelial cells from the anastomotic site. The reendothelialization occurred over the whole graft at one month after transplantation. The neointimal thickening and adventitial inflammation became severe by 3 months after transplantation, but this lessened at 6 months and 12 months, respectively. The rate of CD3 positive cells was very low among the infiltrated inflammatory cells. Conclusion: The fresh-frozen xenogenic artery kept its patency without being greatly influenced by xenogenic immune reaction.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.