Effect Of Intercellular Adhesion Molecule-1 Research Articles

Hyperglycemia Decreases Epithelial Cell Proliferation and Attenuates Neutrophil Activity by Reducing ICAM-1 and LFA-1 Expression Levels.

Delayed repair is a serious public health concern for diabetic populations. Intercellular adhesion molecule 1 (ICAM-1) and Lymphocyte function-associated antigen 1 (LFA-1) play important roles in orchestrating the repair process. However, little is known about their effects on endothelial cell (EC) proliferation and neutrophil activity in subjects with hyperglycemia (HG). We cultured ECs and performed a scratch-closure assay to determine the relationship between ICAM-1 and EC proliferation. Specific internally labeled bacteria were used to clarify the effects of ICAM-1 and LFA-1 on neutrophil phagocytosis. Transwell assay and fluorescence-activated cell sorting analysis evaluated the roles of ICAM-1 and LFA-1 in neutrophil recruitment. ICAM-1+/+ and ICAM-1–/– mice were used to confirm the findings in vivo. The results demonstrated that HG decreased the expression of ICAM-1, which lead to the low proliferation of ECs. HG also attenuated neutrophil recruitment and phagocytosis by reducing the expression of ICAM-1 and LFA-1, which were strongly associated with the delayed repair.

Effect of Intercellular Adhesion Molecule-1 on Adherence Between Mesenchymal Stem Cells and Endothelial Progenitor Cells

To investigate the effects of intercellular adhesion molecule-1(ICAM-1) on the adherence between mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC). MSC and EPC were isolated, cultured and expanded from the 6-8 weeks aged C57BL/6 murine bone marrow by in vitro. Immuno-fluorescence was used to detect the expression of ICAM-1 in MSC group, EPC group and co-cultured MSC and EPC group. The mRNA and protein levels of ICAM-1 were detected by RT-PCR and Western blot respectively, then, the ICAM-1 adherence between MSC and EPC was observed by adding different concentration of neutralizing antibody. The expression of ICAM-1 on surface of MSC and EPC could be detected by cell immunofluorescence method. According to results of the semiquantitative fluorescene detection, the fluorescence strength of MSC+EPC co-cultured group (89.02 ± 24.52) was higher than that of MSC group (31.25 ± 2.95) and EPC group (34.32 ± 5.02), and there was statistical difference between them (P < 0.01), but there was no obvious difference between MSC group and EPC group (P > 0.05). RT-PCR detection showed that the expression levels of ICAM-1 in MSC+EPC co-cultured group were higher than that in MSC group and that in EPC group (P < 0.01), and expression level of ICAM in EPC group was higher than that in MSC group (P < 0.01). Western blot detection showed that the expression level of ICAM-1 protein in MSC+EPC co-cultured group (0.33 ± 0.4) was higher than that in MSC group (0.11 ± 0.01) (P < 0.05) and than that in EPC group (0.19+0.02) (P < 0.05), However, the expression level of ICAM-1 protein in EPC group was higher than that in MSC group (P < 0.05). The test of different concentrations against neutralizing antibody showed that with the increasing of concentration of ICAM-1 neutralizing antibody, the adhesion capability of MSC and EPC was gradually decreasing. The ICAM-1 can mediate the adherence process between MSC and EPC.

Effect of intercellular adhesion molecule-1 on the migration in vitro of murine mesenchymal stem cells and its related mechanism

This study was aimed to investigate the effect of intercellular adhesion molecule-1 (ICAM-1) on the migration in vitro of the murine mesenchymal stem cells (MSC) and its related mechanisms. The migration ability of murine MSC (C3H10T1/2), ICAM-1 transfected MSC (C3H10T1/2-MIGR1-ICAM-1) and empty vector-transfected MSC (C3H10T 1/2-MIGR1) were assayed in vitro by using the transwell system. Briefly, the cells were seeded on the membrane with 8 µm aperture and the fetal bovine serum was used as the chemotactic agent to induce MSC migration. The transmigrated cells were stained by crystal purple as well as DAPI for 8 h and 12 h respectively. The absolute cell numbers were counted and the migration rates of MSC were evaluated in each group. To explore the potential mechanisms which control the migration of MSC, the specific chemical inhibitors of MAPK pathway (SB203580, PD98059 and JNK inhibitor II) were added to the transwell system and the alteration of the MSC migration ability were evaluated at 12 h. The results showed that the migration ability at 8 h and 12 h of the ICAM-1-transfected MSC increased. Both absolute cell number and migration rate of MSC were significantly up-regulated by ICAM-1. Furthermore, the promoting effect of ICAM-1 on migration was partially suppressed by the inhibition of JNK/SAPK pathway. The transmigrated cell numbers and the migration rate decreased with the addition of JNK inhibitor II. However, the ICAM-1 promoting migration of MSC was not suppressed by the inhibitors for ERK/MAPK and p38/MAPK pathway did not work in the present study. It is concluded that ICAM-1 can induce mouse MSC migration in vitro, and the promoting effect is partially dependent on the activation of JNK/SAPK pathway.

Expression and Role of ICAM-1 in the Occurrence and Development of Hepatocellular Carcinoma

Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-κB) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

Effects of Intercellular Adhesion Molecule-1 on Renal Damage in Spontaneously Hypertensive Rats

Aims: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory process and immune response. The aim of the study was to investigate ICAM-1 expression in the kidneys of spontaneously hypertensive rats (SHRs) and the relationship between the level of ICAM-1 and renal damage. Methods: Male Wistar–Kyoto (WKY) rat and SHR models were employed. Blood pressure (BP) was recorded using tail cuff method. Twenty-four hour proteinuria and β2-microglobulin (β2-MG) were measured using biuret method and radioimmunity kits, respectively. Biochemical parameters were measured after the animals were killed. ICAM-1 expression in renal tissue was assessed using western blot and real-time polymerase chain reaction (PCR). Results: It was observed that BP, proteinuria, and urine β2-MG were more increased in SHR groups than that in the same age WKY groups. In SHR groups, BP, proteinuria, and urine β2-MG at the 56th week were significantly higher than that at the 28th week. ICAM-1 protein and mRNA expression in SHR renal tissues was significantly increased in SHR groups compared with the same age in WKY rats. ICAM-l expression was positively correlated with proteinuria and urine β2-MG. Conclusion: This study demonstrated that the renal expression of ICAM-1 was increased in SHR with renal damage, and inflammation may be involved in the hypertensive renal damage.

Angiogenic effect of intercellular adhesion molecule-1

In order to investigate the angiogenic effect of intercellular adhesion molecule-1 (ICAM-1), two parts of experiment were performed. Chick embryo chorioallantoic membrane (CAM) assay was used for in vivo angiogenic research. The chick embryos were divided into 4 groups: ICAM-1 group (divided into 3 subgroups, I, II and III) for screening the angiogenic effect of ICAM-1 by adding different concentrations of ICAM-1 (0.1, 0.2 and 0.3 microg/microL) 5 microL into the chick embryo CAMs on the day 10 after incubation for every subgroup; Anti-ICAM-1 group A (divided into 2 subgroups, I and II) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 microL into the chick embryo CAMs on the day 10 after incubation for every subgroup to evaluate the effect of ICAM-1 on the survival of microvessels through observing whether Anti-ICAM-1 could induce involution of the microvessels on CAMs; Anti-ICAM-1 group B (divided into 2 subgroups, I and II) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 microL into the chick embryo CAMs on the day 6 after incubation for every subgroup to evaluate whether ICAM-1 involved in embryonic angiogenesis through observing the growth of microvessels on CAMs; ICAM-1 or Anti-ICAM-1 was substituted by PBS 5 muL on the day 10 or day 6 after incubation. Three days later, the CAMs were photographed in vivo, excised, sectioned and the number of microvessels was counted. In ICAM-1 group, there was increased number of microvessels arranged radially with "spoked-wheel" pattern around the gelatin sponges. The new microvessels growing perpendicularly to gelatin sponges were observed. The number of the microvessels growing in the CAM mesenchymes around the sponges in 3 subgroups was higher than that in control group (P<0.01), however, there was no significant difference among the 3 subgroups (P>0.05). In anti-ICAM-1 group A, the radially arranged microvessels were very unclear around the sponges contrast to that of ICAM-1 group. Few new microvessels were detected in the center of the sponges. The number of the microvessels growing in the CAM mesenchymes around the sponges in subgroup II was lower than that in control group (P<0.01). There was no significant difference in the number of the microvessels around the sponges between subgroup I and control group (P>0.05). In anti-ICAM-1 group B, the radially arranged microvessels were very unclear around the sponges contrast to that of control group. New microvessels were very scarce in the center of the sponges. The number of the microvessels growing in the CAM mesenchymes around the sponges in the 2 subgroups were less than that in control group (P<0.01), and there was significant difference between the 2 subgroups (P<0.05). It was suggested that ICAM-1 could induce angiogenesis and support the survival of microvessels, and ICAM-1 was involved in embryonic angiogenesis.

Effect of ICAM-1 and LFA-1 in hyperleukocytic acute myeloid leukaemia

Acute hyperleukocytic leukemia [AHL; WBC count >100 x 10(9)/l] is associated with a life-threatening complication. The mechanisms of hyperleukocytosis in acute myeloid leukaemia (AML) remain unclear. However, the interaction of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) plays an important role in the adhesion and migration of normal leukocytes and AML cells. Therefore, effects of ICAM-1 and LFA-1 were studied in hyperleukocytic AML. The adhesion of hyperleukocytic AML blasts and human umbilical vein endothelial cells (HUVECs) was significantly increased compared with that of blasts from non-hyperleukocytic AML (WBC < 100 x 10(9)/l). The adhesion of normal neutrophils and HUVECs treated with hyperleukocytic AML blast supernatant was increased significantly. Finally, we determined the ICAM-1 on the surface of HUVECs treated with the supernatant of hyperleukocytic AML blasts and LFA-1 on hyperleukocytic AML blasts by flow cytometry. It showed that the ICAM-1 expression on the surface of the HUVECs treated with hyperleukocytic AML blast supernatant for 24 h could be increased, and the expression of LFA-1 on hyperleukocytic AML was also increased significantly. Our data show that hyperleukocytic AML blasts stimulate the endothelium to secrete more ICAM-1 and promote their own adhesion to vascular endothelium, suggesting that ICAM-1 and LFA-1 may have a role in hyperleukocytic AML.

Expression of IgSF in salivary adenoid cystic carcinoma and its relationship with invasion and metastasis

The aim of the present work was to study the potential effect of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) of immunoglobulin superfamily on the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). The expressions of ICAM-1, VCAM-1 and NCAM of forty cases with SACC were examined by immunohistochemical methods using respective kits. A significant relation showed between the expression level and histological differentiation, expression of ICAM-1 and VCAM-1 in solid SACC was greatly increased compared with NCAM; SACC with metastatic lymph node or local recurrence displayed significant relationship to the up-regulation of ICAM-1 and VCAM-1, and to the down-regulation of NCAM. It is proposed that ICAM-1 and VCAM-1 may play a role in the invasion and metastasis of SACC. NCAM may be an invasion-resistant adhesion molecule.

REJECTION OF MURINE MELANOMA-CELLS TRANSFECTED WITH THE INTERCELLULAR-ADHESION MOLECULE-1 GENE

The effects of intercellular adhesion molecule-1 (ICAM-1) expression on-tumor rejection and induction of antitumor immunity in a murine melanoma system was studied. K1735 melanoma cells genetically engineered to express the murine ICAM-1 gene were rejected in immunocompetent hosts, and that this rejection was mediated by CD4(+) as well as by CD8(+) T lymphocytes. We also found that ICAM-1 transfected tumor cells provided costimulatory signals to both CD4(+) and CD8(+) T cells in vitro. In addition, immunization of mice with K1735-ICAM-1 transfectants induced protective immunity against the parental ICAM-1-negative tumor. Our findings suggest that ICAM-1 expression on nonimmunogenic tumor cells causes tumor rejection and augments tumor-specific immunity.

Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the CD28 counter-receptor B7.

Although ligation of the CD3/TCR complex initiates an activation signal in T cells, additional costimulatory signals generated during cell-to-cell interactions with APC transduced via ligation of CD11a/CD18 and CD28 by their specific counter-receptor intercellular adhesion molecule (ICAM)-1 and B7, respectively, are required for optimal T cell proliferation and cytokine synthesis. Using soluble IgC gamma 1 fusion proteins of these costimulatory counter-receptors, we have recently shown that unactivated resting CD4+ T cells and Ag-primed CD4+ T cells differ in their response to the costimulation by ICAM-1 and B7. Preferential proliferative responses of resting T and Ag-primed T cells to ICAM-1 and B7, respectively, prompted us to speculate that ICAM-1-induced signals may regulate coupling of the CD28 signaling pathway. Furthermore, both B7 and ICAM-1 are co-expressed on APC and thus, may co-regulate activation-driven maturation of T cells. In this study, we have examined regulatory effects of IgC gamma 1 fusion proteins of B7, ICAM-1, and ICAM-2 (a homologue of ICAM-1) on each other's costimulation. We first demonstrate that TCR-directed costimulation of resting CD4+ T cells with ICAM-1 (ICAM-1 priming) but not ICAM-2 induces increased responsiveness to B7. Priming of CD4+ T cells with ICAM-1 induced higher expression of both CD18 and CD28 than that with either B7 or ICAM-2. Cross-linking of CD28 induced faster and significantly higher cytoplasmic free calcium mobilization response in ICAM-1-primed CD4+ T cells than in resting, B7-primed, or ICAM-2-primed CD4+ T cells. B7 synergized with ICAM-1 but not ICAM-2 to augment proliferative responses of not only resting CD4+ T cells but also those that had been primed with either ICAM. Unlike resting or ICAM-2-primed CD4+ T cells, ICAM-1-primed CD4+ T cells efficiently proliferated in response to the synergistic costimulation of B7 and ICAM-2. In contrast, both ICAM-1 and ICAM-2 inhibit B7-driven proliferation of Ag-primed CD4+ T cells. Thus, B7 and ICAM-1 exert contrasting regulatory effects on the proliferation of CD4+ T cells depending on their state of activation-induced maturation.