1.Chemotaxis of Blood Neutrophils from Patients with Primary Ciliary Dyskinesia.
Young Yull KOH ; Yong Han SUN ; Yang Gi MIN ; Je G CHI ; Chang Keun KIM
Journal of Korean Medical Science 2003;18(1):36-41
Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B4 (LTB4), complement 5a (C5a), and formylmethion-ylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.
Adolescent
;
Chemotactic Factors/pharmacology
;
Chemotaxis*
;
Child
;
Cilia/ultrastructure
;
Comparative Study
;
Complement 5a/pharmacology
;
Dose-Response Relationship, Drug
;
Dynein ATPase/chemistry
;
Human
;
Kartagener Syndrome/blood*
;
Kartagener Syndrome/classification
;
Leukotriene B4/pharmacology
;
Male
;
N-Formylmethionine Leucyl-Phenylalanine/pharmacology
;
Neutrophils/physiology*
;
Neutrophils/ultrastructure
2.Elevated monocyte chemoattractant protein-1 in patients with Behcet's disease.
Ju Ho DO ; Ji Hyun JUNG ; Chan Seok PARK ; Ji Song KO ; Soon Sub KIM ; Hyun Cheul CHOI ; Jang Myung SON ; Do June MIN ; Sung Hwan PARK ; Chul Soo CHO ; Ho Youn KIM ; Wan Uk KIM
Korean Journal of Medicine 2003;65(4):458-466
BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) belongs to C-C subfamily of chemokines, which stimulates the migration of monocytes. MCP-1 exerts various effects on the monocytes, including the induction of integrin and tissue factor, and synthesis of proinflammatory cytokines and arachidonic acid. In this study, we measured the MCP-1 levels in patients with Behcet's disease and evaluated the associations between the levels of MCP-1 and the level of other chemokines and various clinical features of Behcet's disease. METHODS: Serum samples were obtained from 67 patients with Behcet's disease and 30 healthy controls. Simultaneously, whole blood was isolated from patients (n=25) with Behcet's disease and healthy controls (n=11) and cultured in 24 well plates for 48 hours in the absence or presence of lipopolysaccharide (LPS) 5 microgram/mL, phytohaemagglutinin (PHA) 5 microgram/mL, phorbol 12-myristate 13-acetate (PMA) 50 ng/mL + ionomycin 5 microgram/mL. The MCP-1 concentrations were measured in the sera and culture supernatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of serum MCP-1 were 2.5 times higher in patients with Behcet's disease than healthy controls. The patients with Behcet's disease had also higher levels of MCP-1 in the culture supernatants of whole blood cells, stimulated with LPS, but not with either PHA or PMA plus ionomycin, compared to healthy controls. Serum MCP-1 levels (n=67) were strongly correlated with serum RANTES, MIP-1alpha, IL-8 levels in Behcet's disease. In addition, the production of MCP-1 by whole blood culture from Behcet's disease patients (n=25) were also correlated well with those of RANTES, MIP-1alpha, and IL-8, when stimulated with LPS. However, MCP-1 levels in the sera and culture supernatants did not show any association with various clinical features of Behcet's disease including oral ulcer, genital ulcer, erythema nodosum, arthritis, uveitis, intestinal involvement, central nervous system involvement, and vascular thrombosis. CONCLUSION: In the sera and culture supernatants of whole blood stimulated with LPS, MCP-1 levels were higher in patients with Behcet's disease than controls and correlated well with RANTES, MIP-1alpha, IL-8 levels. These results suggest that the activation and migration of monocytes triggered by the increased production of MCP-1 may play a role in the pathogenesis of Behcet's disease.
Arachidonic Acid
;
Arthritis
;
Blood Cells
;
Central Nervous System
;
Chemokine CCL2*
;
Chemokine CCL3
;
Chemokine CCL5
;
Chemokines
;
Cytokines
;
Enzyme-Linked Immunosorbent Assay
;
Erythema Nodosum
;
Humans
;
Interleukin-8
;
Ionomycin
;
Monocytes*
;
Oral Ulcer
;
Thromboplastin
;
Thrombosis
;
Ulcer
;
Uveitis
3.Regulation of CC Chemokines in TDI-Induced Nasal Hyperreactive Rats: Expression of RANTES and Eotaxin mRNA Examined Using Competitive PCR.
Chan Seung HWANG ; Hang PARK ; Seng Ho PARK ; Jung Hoon LEE ; Young Ho HONG ; Hoon KIM ; Hak Hyun JUNG ; Sung Joon PARK
Korean Journal of Otolaryngology - Head and Neck Surgery 1999;42(8):985-992
BACKGROUND AND OBJECTIVES: Chemokines are effective leukocyte chemoattractants and may play an important role in mediating eosinophil recruitment in various allergic conditions in human. Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to the site of allergic inflammation. However, it is not yet known as to whether or not RANTES is associated with selective tissue eosinophilia. The aim of this study is to understand the events involved in selective eosinophil migration into inflammatory sites. MATERIALS AND METHODS: We performed the quantitative analysis of RANTES and eotaxin mRNA expression levels in TDI-induced nasal hyper-reactive rats. Expression levels of RANTES and eotaxin mRNA from inferior turbinate mucosa were examined using competitive PCR in 35 experimental rats and 5 control rats compared with infiltrated eosinophil counts. RESULTS: The quantity of RANTES mRNA increased 3 folds 2 day after provocation, and the infiltrating eosinophils were correlated with the expression levels of RANTES mRNA (p<0.01). The quantity of eotaxin mRNA increased 15 folds 1 day after provocation. These results suggest that RANTES and eotaxin play a role in controlling antigen-induced eosinophil recruitment into the tissue. Eotaxin is a more potent and selective chemoattractant for eosinophils than infiltrating eosinophils, and were correlated with the expression levels of eotaxin mRNA (p<0.01). CONCLUSIONS: Further investigations for chemokine receptor related to eosinophils will provide better understanding of the mechanism involved in selective tissue eosinophilia.
Animals
;
Chemokine CCL5*
;
Chemokines
;
Chemokines, CC*
;
Chemotactic Factors
;
Eosinophilia
;
Eosinophils
;
Humans
;
Inflammation
;
Leukocytes
;
Mucous Membrane
;
Negotiating
;
Polymerase Chain Reaction*
;
Rats*
;
RNA, Messenger*
;
Turbinates
4.Chemotaxis-related factors are expressed abnormally in bone marrow mesenchymal stem cells of multiple myeloma patients.
Hui-Jin HU ; Hua LU ; Xiao-Ming FEI ; Jun-Xia LI ; Jian-Yong LI
Journal of Experimental Hematology 2011;19(1):59-63
This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor (HGF), stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. The mRNA expression levels of HGF, SDF-1, MCP-1 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients were detected by real time quantitative RT-PCR and were compared with that in 9 controls. The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with controls (p < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with controls (p < 0.05). There was no significant difference in the mRNA expression levels of MCP-1 and IL-8 between MM and control cohorts (p > 0.05). It is concluded that BM-MSC from MM patients express HGF, SDF-1, MCP-1, IL-8, but these chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysregulated in MM patients, which may result from the interplay between MM cells and MSC.
Bone Marrow Cells
;
metabolism
;
Cells, Cultured
;
Chemokine CCL2
;
metabolism
;
Chemokine CXCL12
;
metabolism
;
Chemotactic Factors
;
metabolism
;
Hepatocyte Growth Factor
;
metabolism
;
Humans
;
Interleukin-8
;
metabolism
;
Mesenchymal Stromal Cells
;
metabolism
;
Multiple Myeloma
;
metabolism
;
RNA, Messenger
;
genetics
5.The Serum Levels of Interleukin-8, Monocyte Chemoattractant Protein-1, and Macrophage Inflammatory Protein-1 alpha in Patients with Acute Ischemic Stroke and with Atherosclerosis.
Jae Kwan CHA ; Sang Ho KIM ; Jae Woo KIM
Journal of the Korean Neurological Association 2000;18(2):132-137
BACKGROUND: Chemokines are molecules with chemotatic activities on selective leukocyte populations and are sub-grouped into alpha-chemokine acting primarily on PMNL (polymorphonuclear leukocyte) and beta-chemokines attracting mainly lymphocytes and monocytes. We conducted a prospective study to investigate the serum levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1 alpha in patients with acute ischemic stroke and carotid atherosclerosis. METHODS: Serum was sampled from patients with acute ischemic stroke (<24hrs), with persistent ischemic neurological deficits associated with atherosclerosis (>1 month), and from normal subjects without a history of vascular disease. Concentrations of chemokines were measured by enzyme linked immunosorbent assay ( ELISA ). RESULTS: Compared with carotid atherosclerotic patients and control subjects, the serum levels of IL-8 were significantly elevated in those with acute ischemic stroke. The serum levels of MCP-1 in patients with large artery disease were higher than those in patients with small vessel disease and cardioembolism. CONCLUSIONS: This study suggested that IL-8 can be involved in acute ischemic stroke and MCP-1 plays a role in the pathogenesis of atherosclerosis.
Arteries
;
Atherosclerosis*
;
Carotid Artery Diseases
;
Chemokine CCL2*
;
Chemokines
;
Chemokines, CC
;
Cytokines
;
Enzyme-Linked Immunosorbent Assay
;
Humans
;
Interleukin-8*
;
Interleukins
;
Leukocytes
;
Lymphocytes
;
Macrophage Inflammatory Proteins*
;
Macrophages*
;
Monocytes*
;
Prospective Studies
;
Stroke*
;
Vascular Diseases
6.Microvessel counts and the expressions of chemotactic factors in the pathological scar tissues.
Li QIAN ; Bai-Cheng ZHAO ; Li PI ; Qing LU
Journal of Central South University(Medical Sciences) 2005;30(3):340-348
OBJECTIVE:
To explore the microvessel counts and the expressions of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 ( MIP-1) alpha mRNA in the pathological scar tissues.
METHODS:
Immunohistochemical method of avidin-biotin complex was used for microvessel counts on the routinely formalin-fixed and paraffin-embedded sections of specimens of hypertrophic scars, keloids, normal skin, and surgical scar, and in situ hybridization for the expressions of IL-8, MCP-1, MIP-1alpha mRNA.
RESULTS:
The microvessel counts as well as the positive rates and the scorings of IL-8, MCP-1, and MIP-1alpha mRNA were significantly higher in pathological scars than those in the normal skin and surgical scar (all P < 0.05). The microvessel counts were significantly higher in the positive cases of IL-8, MCP-1 and MIP-1alpha mRNA than those in the negative ones (P < 0.05). The close positive correlations were found among the microvessel counts and the expressive scorings of 3 factors (P < 0.05). The close positive correlations were also found among the expressive scorings of IL-8, MCP-1, and MIP-1alpha mRNA in pathological scars. Microvessel counts were significantly higher in hypertrophic scars with the course less than 1 year than those with the course more than 1 year.
CONCLUSION
IL-8, MCP-1 and MIP-1alpha play important roles in promoting the neovascularization of pathological scars.
Adolescent
;
Adult
;
Burns
;
complications
;
Capillaries
;
metabolism
;
Chemokine CCL2
;
biosynthesis
;
genetics
;
Chemokine CCL3
;
Chemokine CCL4
;
Cicatrix
;
etiology
;
metabolism
;
Female
;
Humans
;
Interleukin-8
;
biosynthesis
;
genetics
;
Macrophage Inflammatory Proteins
;
biosynthesis
;
genetics
;
Male
;
Middle Aged
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Skin
;
blood supply
7.Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn's Disease.
Kyoichi KATO ; Ken FUKUNAGA ; Koji KAMIKOZURU ; Shinichiro KASHIWAMURA ; Nobuyuki HIDA ; Yoshio OHDA ; Naohisa TAKEDA ; Koji YOSHIDA ; Masaki IIMURO ; Yoko YOKOYAMA ; Risa KIKUYAMA ; Hiroto MIWA ; Takayuki MATSUMOTO
Gut and Liver 2011;5(1):37-45
BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.
Antibodies
;
Antibodies, Monoclonal
;
Chemokine CCL2
;
Chemokine CCL5
;
Chemokines
;
Crohn Disease
;
Cytokines
;
Humans
;
Immune System
;
Interferons
;
Interleukin-10
;
Interleukin-13
;
Interleukin-6
;
Interleukin-8
;
Interleukins
;
Lymphocytes
;
Macrophages
;
Mesalamine
;
Remission Induction
;
T-Lymphocytes, Regulatory
;
Tumor Necrosis Factor-alpha
;
Infliximab
8.Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis.
Shufen CHEN ; Zhihong LIU ; Huiping CHEN ; Hong ZHOU ; Jianping WANG ; Leishi LI
Chinese Medical Journal 2002;115(9):1301-1307
OBJECTIVETo study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment.
METHODSTwelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed.
RESULTSAlthough steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN.
CONCLUSIONSThe efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.
Adolescent ; Adrenal Cortex Hormones ; administration & dosage ; Adult ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Biopsy ; Chemokine CCL2 ; analysis ; Chemokine CCL3 ; Chemokine CCL4 ; Chemokines, CC ; analysis ; Child ; Cyclophosphamide ; administration & dosage ; Female ; Glomerulonephritis ; drug therapy ; immunology ; pathology ; Humans ; Kidney Glomerulus ; chemistry ; pathology ; Macrophage Inflammatory Proteins ; analysis ; Male ; Middle Aged
9.IFN -r Enhances Induction of Chemokines Mig and IP10 mRNA from THP - 1 Cells Stimulated with Lipoarabinomannan.
Korean Journal of Immunology 1999;21(4):343-351
Lipoarabinomannans (LAM) is believed as a potential virulence factor of Mycobacterium tuberculosis. LAM exhibits marked differences in biological activities depending on the types, arabinofuranosyl-terminated LAM (AraLAM) derived from a rapidly growing Mycobacterium sp. and heavily mannosylated LAM (ManLAM) derived from the Erdman strain. Collaboration between macrophages and T cells, especially macrophage activation by gamma interferon (IFN-r) and chemoattraction of T cells at the very inflammatory foci would be essential in defence against M. tubercu/osis. Chemokines Mig and IP-10 are inducible by IFN-r from macrophages and have been shown to act in vitro as T cell chemoattractants. However, little is known of LAMs capacity to induce chemokines Mig and IP-10 in macrophages. In this experiment, Mig and IP10 mRNA was expressed in the delayed-type hypersensitivity (DTH) against BCG in BCG-immune mice. In some experiments, both Mig and IP-10 mRNA was evidently induced with different time courses in THP-1 cells stimulated with whole live M. tubercu/osis H37Rv (Erdman). To investigate whether Mig and IP-10 genes are differentially induced depending on the type of LAM, PCR amplification was used to detect mRNA of Mig and IP-10 from the THP-1 human monocytic cells stimulated with LAM. AraLAM, but not ManLAM, induced weakly Mig and IP-10 mRNA in the THP-1 cells. The induction of Mig and IP-10 was dependent upon the dose of AraLAM and exhibited different time courses. The mRNA for Mig and IP-10 was induced within 2 hr and 4 hr from the initiation of treatrnent and has disappeared by 8 hr and 24 hr under the experimental conditions used in this study, respectively. IFN-y at 100 U/ml, but not at 10 U/ml, was itself a good stimulus of both Mig and IP- 10 expression, and synergized with either AraLAM or ManLAM for induction of both Mig and IP-10. The expression patterns of MCP-3 were somewhat similar to those of Mig and IP10 in all of the experiments. These data indicate that IFN-r may contribute to effective macrophage function if macrophages are not fully affected by ManLAM, and chemokines Mig and IP-10 may a role in recruitment of T cells at inflammatory foci of tuberculosis.
Animals
;
Chemokines*
;
Chemotactic Factors
;
Cooperative Behavior
;
Humans
;
Hypersensitivity
;
Interferons
;
Macrophage Activation
;
Macrophages
;
Mice
;
Mycobacterium
;
Mycobacterium bovis
;
Mycobacterium tuberculosis
;
Polymerase Chain Reaction
;
RNA, Messenger*
;
T-Lymphocytes
;
Tuberculosis
;
Virulence
10.Alteration of tazarotene induced gene-2 expression in psoriasis vulgaris.
Yan ZHENG ; Su-ju LUO ; Wei-hui ZENG ; Zhen-hui PENG ; Sheng-shun TAN ; Yan-ping XI
Journal of Southern Medical University 2008;28(10):1792-1794
OBJECTIVETo investigate the role of tazarotene induced gene-2 (TIG2) in psoriasis vulgaris.
METHODSTIG2 protein and mRNA expressions in normal tissues, psoriatic lesions and uninvolved skin tissues were detected by immunohistochemistry and in situ hybridization, respectively.
RESULTSTIG2 protein and mRNA were expressed in all the layers of normal and uninvolved epidermis. TIG2 expression was detected in the upper layers of the stratum spinosum of the marginal region of the psoriatic lesions, but not in the central area of the lesions. TIG2 expression was significantly lower in the basal layers of the central area of the paoriasis than that in the normal skin and uninvolved tissues (P < 0.01), and also lower in the marginal regions of the lesions (P < 0.01).The suprabasal layers of the marginal region in the lesion showed significantly lower TIG2 expression than the central area of the lesion (P < 0.01).
CONCLUSIONTIG2 may maintain the normal differentiation of epidermal keratinocytes and implicate in the pathogenesis and development of psoriasis vulgaris.
Adolescent ; Adult ; Chemokines ; Chemotactic Factors ; biosynthesis ; genetics ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; genetics ; Keratinocytes ; metabolism ; Male ; Middle Aged ; Psoriasis ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics