Endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 is suppressed by postbypass plasma containing increased soluble intercellular adhesion molecule 1 and vascular cell adhesion molecule 1

OBJECTIVE: Endothelial cell dysfunction has been implicated in the inflammatory response to cardiopulmonary bypass, and the upregulation of endothelial cell expression of adhesion molecules might promote leukocyte extravasation in vivo. Soluble endothelial cell adhesion molecules are increased after bypass. The aim of this study was to investigate the relationship between endothelial cell-surface expression of adhesion molecules and their concentration in plasma after coronary artery bypass grafting. METHODS: Ten patients undergoing coronary artery bypass with cardiopulmonary bypass had 5 plasma samples taken at defined intervals before, during, and after cardiopulmonary bypass. Plasma was incubated with human umbilical vein endothelial cell monolayers, and expression of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 on the surface of human umbilical vein endothelial cell monolayers was measured by means of enzyme-linked immunosorbent assay. Plasma soluble adhesion molecules, C-reactive protein, interleukin 8, interleukin 10, transforming growth factor beta1, and neutrophil counts were determined for each patient. RESULTS: Markers typical of acute inflammation (ie, interleukin 8, neutrophils, and C-reactive protein) were all increased after bypass. Soluble plasma intercellular and vascular cell adhesion molecule 1 (but not E-selectin) were increased after bypass. However, endothelial cell expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 (but not E-selectin) were significantly decreased by exposure to postbypass plasma. Additionally, postbypass plasma inhibited interleukin 1beta-stimulated endothelial cell expression of vascular cell and intercellular adhesion molecule 1. Interleukin 10 and transforming growth factor beta1, both of which are known to inhibit endothelial cell adhesion molecule expression, were respectively increased 10-fold and 3-fold (P <.05) after bypass. CONCLUSIONS: Despite containing increased soluble intercellular and vascular cell adhesion molecule 1, postbypass plasma inhibits endothelial cell expression of intercellular and vascular cell adhesion molecule 1. Upregulated vascular expression of adhesion molecules might not be essential for endothelial activation after bypass.     

Cell surface expression and serum levels of intercellular adhesion molecule-1 in renal cell carcinoma

Intercellular adhesion molecule-1 (ICAM-1) is the natural ligand of the T-lymphocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen-1). ICAM-1 is involed in target cell recognition by T-lymphocytes, LAK cells and natural killer cells. The molecule has also been detected on a variety of normal cells and on human tumors. Renal cell carcinoma (RCC) is one of the few tumors that respond to immunotherapy, but clinical results are generally disappointing. We therefore analyzed, by immunohistochemistry, the expression of ICAM-1 in pairs of normal kidneys, RCC, and RCC metastases. Moreover, serum ICAM-1 was determined in RCC patients and compared with surface expression of cell-bound ICAM-1. Strong glomerular expression of ICAM-1 was observed in all specimens of normal kidney examined. Proximal tubuli were weakly stained in the majority of specimens. Of the tumors, 80% stained positive for ICAM-1. Although ICAM-1 was detected on the majority of extrarenal tumor specimens examined, staining was generally weaker in the metastases. Patients without metastases at initial presentation more frequently expressed ICAM-1 in their primary tumors than did patients with metastases. Levels of serum ICAM-1 (sICAM-1) were significantly higher in RCC patients than in controls with non-malignant renal diseases. Patients with an unfavorable prognosis, e.g. with advanced tumor stage or metastasis at initial presentation, had higher levels of sICAM-1 than patients with low-grade and/or low-stage tumors. An inverse correlation was observed between expression of ICAM-1 in tumors and levels of sICAM-1. On the basis of our data we suggest that cell-bound or soluble ICAM-1 is correlated with tumor-host interaction in RCC.     

Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage

OBJECT: Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule-1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1-2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. METHODS: Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, < 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade-matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade-matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). CONCLUSIONS: These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.     

Tubular and interstitial expression of ICAM-1 as a marker of renal injury in IgA nephropathy

BACKGROUND: The upregulated renal expression of intercellular adhesion molecule 1 (ICAM-1) is associated with glomerular and interstitial infiltration of leukocytes. AIM: To test the hypothesis that renal expression of ICAM-1 may be predictive in the highly variable IgA nephropathy (IgAN). METHODS: ICAM-1 (CD54) in tubular epithelium and interstitial leukocytes, macrophages (CD14), and T cells (CD3) were assessed using avidin-biotin-peroxidase in renal biopsy specimens from 45 patients with IgAN and from 29 patients with no glomerulonephritis. RESULTS: In IgAN, tubular ICAM-1+ was seen in 25 of 45 (55%) biopsy specimens, associated with glomerular hypercellularity, glomerulosclerosis involving less than 50% of the glomerular area, interstitial cellular infiltration, tubular atrophy, and proteinuria (U = 44, p = 0.005). Interstitial ICAM-1+ leukocytes were correlated with glomerulosclerosis involving less and more than 50% of the glomerular area, tubular atrophy, interstitial fibrosis, and serum creatinine concentration (r = 0.6343, p < 0.001). In patients with an increase of 50% in the serum creatinine concentration, interstitial ICAM-1+ leukocytes and CD14+ and CD3+ cells were significantly more numerous than in patients with a stable creatinine concentration. In patients with no glomerulonephritis, tubular ICAM-1+ was seen in 7 of 29 (24%) biopsy specimens, inversely correlated with the number of normal glomeruli and associated with glomerulosclerosis covering more than 50% of the glomerular area, tubular atrophy, and creatinine. CONCLUSIONS: Tubular and interstitial expression of ICAM-1 can be a marker of tubulointerstitial disturbance in IgAN. Interstitial ICAM-1 may be an adverse predictor of disease progression.     

Assessment of certain neutrophil receptors, opsonophagocytosis and soluble intercellular adhesion molecule-1 (ICAM-1) following thermal injury.

Polymorphonuclear leukocytes (PMLs) play a key role in host defense, and phagocyte dysfunction has been associated with increased susceptibility to infections in patients with thermal injury. Intercellular adhesion molecule-1 (ICAM-1) plays a role in leukocyte accumulation and extravasation. Therefore, the aim of the present study was to assess the PMLs expression of opsonin receptors: Fc gamma RIII, CR1 and CR3; opsonophagocytosis of PMLs and plasma soluble ICAM-1. Flow cytometric analysis (FCM) was used to study PMLs expression of IgG Fc-receptor III (Fc gamma RIII) as well as the complement receptors CR1 (receptor for C3b) and CR3 (receptor for C3bi) in 23 patients with large burns. Analysis of PML complement- and immunoglobulin-mediated phagocytosis of Candida albicans were performed in parallel using the phagocytic index. Plasma sICAM-1 was determined using ELISA. This study revealed a significant increase, with variable degrees, in CR1 and CR3-dependent fluorescence, complement-mediated phagocytosis of C. albicans and plasma sIGAM-1 that started at day 2 and remained for about 20 days before normalization. In contrast, Fc gamma RIII-dependent fluorescence and Ig-mediated phagocytosis were significantly decreased versus the control values. These results demonstrate significant changes of PMLs opsonin receptors expression and opsonophagocytosis documenting systemic activator of PMLs after large burns. In addition, elevation of plasma sICAM-1 may enhance the harmful effect of neutrophil activation through leukocyte accumulation and extravasation through endothelial damage in skin and in lung.     

The adherence of endothelial cells to Dacron induces the expression of the intercellular adhesion molecule (ICAM-1).

The intercellular adhesion molecule (ICAM-1) is a glycoprotein expressed by endothelial cells activated by cytokines. The lymphocyte-function-associated antigen (LFA-1) is an integrin expressed by activated white blood cells. Together, this receptor-ligand pair is responsible, in part, for the localization of neutrophils at sites of inflammation. Using an in vitro model, the authors studied the binding of antibodies against ICAM-1 by human saphenous vein endothelial cells (HSVEC) adherent to Dacron and control cultureware. After adherence to Dacron pretreated with fibronectin, 24% more HSVEC-bound antibody against ICAM-1 compared with HSVEC on controls. In contrast, 90% more HSVEC adherent to Dacron incubated with whole blood bound anti-ICAM-1 antibodies. These cells bound 17.7-fold greater amounts of antibody compared with HSVEC on controls. Pretreating Dacron with plasma resulted in no increase in antibody binding compared with control. Our studies suggest that the cellular components of blood in contact with Dacron create a microenvironment that activates HSVEC and enhances ICAM-1 expression. Induction of this adhesion molecule may play a pivotal role in the migration and localization of leukocytes at the site of the vascular prosthesis.     

Serum levels of soluble Fas and disease activity in patients with IgA nephropathy

Using a sandwich ELISA, we studied 48 patients with IgA nephropathy and 10 patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (non-IgA PGN) to determine if levels of serum soluble Fas (s-Fas) might reflect the disease activity. The levels of serum s-Fas in patients with the advanced stage of IgA nephropathy were significantly higher than those in patients with the mild stage of the disease, in non-IgA PGN or in healthy controls. The results showed that advanced stage IgA nephropathy patients who showed heavy proteinuria and the presence of urinary casts revealed high levels of serum s-Fas. It was thus suggested that the measurement of serum s-Fas is useful in evaluating the degree of renal injury in patients with IgA nephropathy.     

The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells

BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.     

Correlation between the serum values of soluble intercellular adhesion molecule-1 and total sialic acid levels in patients with breast cancer

BACKGROUND: In this study, we aimed to investigate serum total sialic acid (TSA) and soluble intracellular adhesion molecule-1 (sICAM-1) levels in breast cancer patients to find a correlation with the cancer stage. METHODS: The parameters from sera of 61 patients with breast cancer were measured. The concentrations of serum sICAM-1 and TSA were measured in serum samples from 61 patients with breast cancer and 25 healthy control subjects using enzyme-linked immunoassay and thiobarbituric acid method. RESULTS: Mean serum sICAM-1 and TSA levels were significantly higher in the total patient group than in the control group (p < 0.001). Thus, the correlation between TSA and sICAM-1 became more significant in metastatic breast cancer. There were significant positive correlations between TSA and sICAM-1 in stage I+II (r = 0.59, p < 0.05), stage III (r = 0.47, p < 0.05), and stage IV (r = 0.89, p < 0.01), and total patient group (r = 0.56, p < 0.001). CONCLUSION: SerumsICAM-1 and TSA levels were higher in patients with breast cancer, than that of the control group, and also in the metastatic breast cancer group. Significant correlations between serum sICAM-1 and TSA may reflect the similar function of these molecules as adhesion molecules, and their roles in the carcinogenesis of breast cancer as well as metastasis.     

颅脑损伤后血清中sICAM-1和IL-1β含量变化的意义

目的 动态观测急性颅脑损伤患者血清中sICAM-1和IL-1β含量的变化．探讨其临床意义。方法 按入院先后随机选取25例被CT证实的颅脑损伤患者，按照入院时、24．48．96小时四个时间段分别采集血标本，应用双抗体夹心酶联免疫吸附法（ELISA）测定sICAM-1和IL-1β的含量．并与对照组比较。结果 颅脑损伤患者早期sICAM-1含量较对照组无变化，在48小时明显升高，并持续升高至96小时（P〈0．05）。sICAM-1含量与损伤程度无关，而与预后相关。皿清中IL-1β含量于入院时就有明显升高（P〈0．05），IL-1β升高不仅与损伤程度有关，而且与预后也密切相关。血清中IL-1β含量与sICAM-1含量相关。结论 血清中sICAM-1和IL-1β参与了颅脑后继发性脑损伤，sICAM-1和IL-1β升高反映了颅内的炎症反应。     

Potential value of soluble intercellular adhesion molecule-1 in the serum of patients with bladder cancer

INTRODUCTION: The potential value of serum levels of intercellular adhesion molecule-1 (ICAM-1) in the staging and pathological nature of bladder cancer was investigated in this study. MATERIALS AND METHODS: A total of 90 patients (mean age 64.5 +/- 7.1) having transitional cell carcinoma of the bladder and 30 control patients (mean age 64.0 +/- 5.5) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery, at the same hour of the day. RESULTS: The preoperative sICAM-1 levels were found to be 46.2 +/- 14.7 and 28.0 +/- 7.8 ng/ml in the tumor group and the control group respectively, which is significantly higher (p = 0.00). The ICAM-1 levels were not different in the invasive tumor group (36 patients) and the superficial tumor group (54 patients; 47.3 +/- 13.8 ng/ml in the invasive group and 45.5 +/- 15.3 ng/ml in the superficial tumor group; p = 0.520). The serum levels of sICAM-1 were significantly higher in grade III tumors than grade I and II tumors (62.0 +/- 8.7, 38.4 +/- 11.9 and 42.2 +/- 8.2 ng/ml respectively; p = 0.000). The mean serum sICAM-1 levels in tumors >3 cm and <3 cm were found to be 52.6 +/- 15.8 and 40.7 +/- 11.0 ng/ml respectively which is statistically significant (p = 0.000). CONCLUSIONS: In this study, serum ICAM-1 levels were found to be related to tumor presence, grade and size. Larger series are needed for the thorough understanding of the role of ICAM-1 in bladder cancer.     

Immunohistochemical studies of glomerular extracellular components in repeated renal biopsies of patients with IgA nephropathy.

Immunohistochemical and light microscopic examinations were carried out to assess the correlation between the progression of glomerular lesions and changes in the intensity of glomerular extracellular components such as type IV and I collagens, laminin and fibronectin, and of IgA deposits in repeated renal biopsies of patients with IgA nephropathy. By light microscopy, the percentage of glomeruli showing glomerular mesangial expansion or sclerosis was found to be significantly higher in the second renal biopsy. Type IV collagen, laminin and fibronectin were also marked in the expanded glomerular mesangium in the second biopsy. Although these components were not observed in the global sclerotic glomeruli, type I collagen was detected in such areas of patients with IgA nephropathy. Patients who revealed high percentages of glomerular sclerosis associated with marked type IV collagen, laminin, fibronectin and/or type I collagen, had high levels of proteinuria and progressive deterioration of renal function. It is concluded that hyperproduction of the above extracellular components mainly in the glomerular mesangium is closely linked to the progression of glomerular lesions in patients with IgA nephropathy.     

Interleukin-6 and soluble intercellular adhesion molecule-1 in renal cancer patients and cultured renal cancer cells

Serum interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assay in 62 renal cancer patients: 30 were tumor-free after radical nephrectomy and 32 presented with metastatic disease. Serum IL-6 was undetectable in all but one of the tumor-free patients, whereas 41% (13 of 32) of the metastatic patients presented serum IL-6 levels. Furthermore, there was a significant correlation between serum IL-6 levels and a shorter overall survival (p = 0.009). Moreover, serum sICAM-1 levels were significantly higher (p = 0.05) in the metastatic patients with detectable serum IL-6 than in those without IL-6, suggesting a possible link between IL-6 and sICAM-1. The probability of a shorter overall survival was greater in the metastatic patients with both serum IL-6 and elevated sICAM-1 levels (>635 ng/ml), than in those with elevated sICAM-1 but without IL-6 (p = 0.01). The production of IL-6 by 16 freshly dissociated renal cancer cells cultured in vitro was also observed. It appeared that IL-6 levels did not correlate with the expression and release of ICAM-1 by cultured cells, although the highest values of ICAM-1 release were found in cultures synthesizing the highest values of IL-6. In conclusion, in vivo presence of serum IL-6 and elevated sICAM-1 levels is related to an unfavorable prognosis; it can be speculated that the cells capable of releasing high levels of sICAM-1 and IL-6 may negatively influence the antitumor response.     

Higher serum levels of soluble intracellular cell adhesion molecule‐1 and soluble vascular cell adhesion molecule predict peripheral artery disease in haemodialysis patients

Aim: Serum levels of soluble intracellular cell adhesion molecule‐1 (sICAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM) and monocyte chemotactic protein 1 (MCP‐1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. Method: A total of 112 HD patients were included and PAD was diagnosed using the ankle‐brachial index and Doppler ultrasound. Serum levels of sICAM‐1, sVCAM‐1 and MCP‐1 were assayed using enzyme linked immunosorbent assay. Results: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM‐1 and sICAM‐1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3–65.5) and 2.7 (95% CI 1.2–21.8) respectively. Using sVCAM‐1 and sICAM‐1 for diagnosis of PAD in HD patients, sVCAM‐1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM‐1 and sICAM‐1 had a sensitivity of 89.3% and a specificity of 40%. MCP‐1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A‐V access flow. Conclusion: sVCAM‐1 and sICAM‐1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A‐V access flow. Our results showed that sVCAM‐1 and sICAM‐1 may be used as screening markers for PAD in HD patients.     

The association of WISP-1 expression in IgA nephropathy patients with renal interstitial fibrosis

Objective To investigate the relationship between the expression of Wnt induced secreted protein-1 (WISP-1) and the fibrosis of renal biopsy tissue in IgA nephropathy (IgAN) patients. Methods Fifty-three patients firstly diagnosed as IgA nephropathy by renal biopsy were included and classified according to Oxford and Lee's classification. Sixteen patients with MCD entered the fibrosis negative control group, and fourteen healthy adults entered the normal control group. The expression of WISP-1 in renal tissues and serum of all subjects were detected by immunohistochemistry and ELISA respectively. Results Immunohistochemistry results showed that WISP-1 was not expressed in MCD patients and normal human kidney tissues, which was abundantly deposited in renal tissue of patients with focal proliferative IgAN with renal interstitial fibrosis. The serum level of WISP-1 in IgAN patients was significantly higher than that in normal subjects (P=0.015) and MCD patients (P=0.030). In the subgroup analysis of IgAN renal fibrosis, the serum concentration of WISP-1 of fibrosis grade between 0-10% (F1 group) and fibrosis＞25% (F3 group) were significantly higher than that in the normal group and the MCD group (all P＜0.05). There was no significant difference between F2 group (10%＜fibrosis≤25%) and normal group or MCD group (P＞0.05). Conclusions The expression of WISP-1 in serum and renal tissue of renal interstitial fibrosis IgAN patients is higher than that of normal and MCD patients without renal fibrosis, and the IgAN patients' serum level of WISP-1 is significantly increased in fibrosis lower score group. The expressions of WISP-1 in serum and renal tissue are related to the occurrence of IgAN renal interstitial fibrosis, in which WISP-1 may play an important role as an early precursor factor in the pathogenesis of IgAN renal interstitial fibrosis.     

Bound and soluble adhesion molecule and cytokine levels in patients with severe burns

We measured endotoxins, inflammatory cytokines and soluble adhesion molecules in the blood of 17 severe burn patients to determine the involvement of these factors in the pathophysiology of severe burns. All seventeen patients had burns with a total burn surface area of 20% or more and a burn index of 15% or more. Endotoxin was measured by an endotoxin-specific assay and tumor necrosis factor-alpha, interleukin 6 and interleukin 8 and soluble adhesion molecules were measured by enzyme-linked immunosorbent assay. CD11a, CD11b and CD18, measured by flow cytometry, were elevated in the non-surviving group, the septic shock group and the multiple organ dysfunction syndrome group, suggesting a close connection between these adhesion molecules and burns complicated by infection. Soluble adhesion molecules were found to indirectly reflect the level of endothelial cell adhesion molecules, suggesting that inflammatory cytokines may also be involved in their production.     

Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid haemorrhage in rats

Summary In order to study how immune-inflammatory responses are involved in the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH), the kinetics of expression of the intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor, were studied on the cerebral arteries following SAH in rats.The SAH was induced by intracisternal injection of arterial blood. The rats were sacrificed at specified times: immediately after induction of SAH to seven days after SAH. Cryostat sections of the basilar artery (BA) were prepared and incubated with anti-rat ICAM-1 antibody. Morphometric analysis of the BA revealed a significant narrowing of the luminal diameter on Day 2 following SAH. While in the non-treated normal animals, no nor only weak expression of ICAM-1 was observed on the endothelial layer of the BA, there was greater expression of ICAM-1 on the endothelial layer of the BA in SAH rats, and the expression was observed also in the medial layer of the artery from Day 2 to Day 5 following SAH.The present results indicate that SAH really causes responses in the cellular immunity not only in the endothelial layer, but also in the medial layer of the artery as a target of immune damage, which is presumed to be one of the important steps in the development of cerebral vasospasm.     

The correlation between serum levels of oxidative stress indicators and renal interstitial fibrosis in patients with IgA nephropathy

Objective To investigate the relationship between serum levels of oxidative stress indicators and the degree of renal interstitial fibrosis in patients with IgA nephropathy (IgAN). Methods Seventy eight patients with confirmed primary IgAN in General Hospital of Ningxia Medical University from January 2013 to December 2014 were enrolled. The patients were divided into T0 group (n=30), T1 group (n=26) and T2 group (n=22) according to the grade of tubular atrophy/interstitial fibrosis of Oxford pathological classification criteria for IgAN in 2009. Meanwhile, thirty cases of health examiner were enrolled as control subjects. The levels of serum malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were detected by xanthine oxidase method, thiobarbituric acid spectrophotometry method, ultraviolet spectrophotometry method, chemical colorimetric method, respectively. The levels of serum advanced oxidation protein products (AOPPs), transforming growth factor beta 1 (TGF-β1), monocyte chemotactic protein 1 (MCP-1), transforming growth factor alpha (TGF-α), interleukin 6 (IL-6) and hypoxia inducible factor 1 alpha (HIF-1α) were detected by enzyme linked immunosorbent assay (ELISA) in all groups. Spearman correlation analysis was used to analyze the correlation between serum oxidative stress indicators and traditional risk factors of tubular atrophy/renal interstitial fibrosis. Multivariable linear regression analysis was used to analyze the correlation between oxidative stress indicators and degree of renal tubular atrophy/renal interstitial fibrosis. Results There were differences in serum levels of AOPPs, MDA, SOD, CAT and GSH-Px in IgAN patients with different degrees of renal interstitial fibrosis (all P﹤0.05). With the increase of renal interstitial fibrosis, the levels of AOPPs and MDA increased gradually, while the levels of SOD, CAT and GSH-Px decreased gradually. Serum AOPPs, MDA, SOD, CAT, GSH-Px concentration in IgAN patients were correlated with the mean arterial pressure (MAP), total blood protein (TP), albumin (Alb), Scr, uric acid (UA), 24-hour urinary protein volume and estimated glomerular filtration rate (eGFR). Multivariate regression analysis showed that the AOPPs levels of blood were positively correlated with MAP, Scr, UA and 24-hour urinary protein (all P﹤0.01), and negatively correlated with TP, Alb, eGFR (all P﹤0.05). The serum levels of AOPPs and MDA in IgAN patients were positively correlated with the levels of TGF-β1, MCP-1, TGF-α, IL-6 and HIF-1α. The levels of SOD, CAT and GSH-Px were negatively correlated with the levels of TGF-β1, MCP-1, TGF-α, IL-6 and HIF-1α. Multivariate stepwise regression analysis showed that the degree of renal interstitial fibrosis in IgAN patients was positively correlated with serum AOPPs level (β=0.285, P=0.001), negatively correlated with CAT (β=-0.346, P﹤0.001), GSH-Px (β=-0.303, P﹤0.001). Conclusions The level of serum oxidative stress in IgAN patients is elevated and positively correlated with the degree of renal interstitial fibrosis, suggesting that oxidative stress may be involved in the occurrence and development of renal interstitial fibrosis.