Granulocyte Activation and Adhesion Molecules During Hemodialysis With Cuprophane and a High-Flux Biocompatible Membrane

114

Besides cell-bound adhesion molecules, which are of fundamental importance to a large number of physiological and pathological processes, soluble forms of adhesion molecules have been detected in the circulating blood in recent years. Circulating soluble adhesion molecules appear to be biologically active, and raised levels have been reported in a variety of disorders. In the present study, we used ELISA to measure the serum levels of four soluble adhesion molecules in 23 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 17 on chronic hemodialysis (HD) and 18 healthy controls having a similar mean and distribution of ages. The investigated soluble (s) molecules included intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin and sP-selectin. sICAM-1 was found to be elevated in patients with CRF (p < 0.05), on CAPD (p < 0.02) and HD (p < 0.0001) compared with the controls but levels did not differ between the three patient groups. The higher sVCAM-1 values found in CRF (p < 0.02), CAPD (p < 0.05) and HD (p < 0.0001) as compared to controls again failed to differentiate the three groups of patients. Soluble E-selectin was also raised in the three groups (p < 0.0001) with no difference between them. Increased sP-selectin was found in CRF (p < 0.05), CAPD (p < 0.02) and in HD patients (p < 0.0001) compared to controls, and levels in HD were significantly higher (p < 0.02) than in CRF patients. Predialysis serum molecule levels did not differ between HD patients treated with cuprophan or with polyacrylonitrile dialyzers. HD sessions with both dialyzers had no effect on sICAM-1, while a decrease (p < 0.02) in sP-selectin was found after dialysis with cuprophan. In undialyzed patients with CRF, regression analysis showed a strong linear correlation between serum creatinine and serum levels of each soluble molecule. These results demonstrate that serum levels of soluble adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin are elevated in both undialyzed patients with CRF and patients on CAPD or HD. The elevated serum levels of these proteins probably reflect inadequate clearance as well as enhanced synthesis/release.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Serum Levels of Soluble Adhesion Molecules in Chronic Renal Failure and Dialysis Patients

Bonomini¹,

Reale²,

Santarelli³

et al. 1998

114

“…The degree of activation depends on the flow design of the dialyzers used, on the composition and geometry of the dialysis membrane and on rheological factors derived from blood circulation. Previous studies have suggested that an increased granulocyte expression of CD11b/18 may be caused by complement activation and may enhance granulocyte adhesiveness to the endothelium, leading to granulocytopenia [1, 2, 3, 4, 5]. Regenerated cellulose (RC) membranes, which are complement-activating membranes, activate leukocytes and upregulate CD11b/18 on leukocytes.…”

Section: Introductionmentioning

confidence: 99%

Expression of Fc Gamma Receptor III (CD16) on Monocytes during Hemodialysis in Patients with Chronic Renal Failure

Kawanaka

Nagake

Yamamura

et al. 2001

Background/Aims: Circulating CD14+CD16+ monocytes, a potent phagocytosing and antigen-presenting monocyte population, have been reported to be expanded in patients on hemodialysis (HD). In this study, changes in the population of CD14+CD16+ monocytes were analyzed during a single session of HD therapy, and the influence of dialyzer membrane materials on these monocytes was investigated. Methods: Nine patients were hemodialyzed using regenerated cellulose (RC) membranes and thereafter polysulfone (PS) membranes. Peripheral blood cells were taken from these subjects, and these cells were stained with anti-CD14 and anti-CD16 antibodies. The percentages of CD14- and CD16-expressing monocytes were analyzed by two-color flow cytometric analysis. Moreover, the serum soluble CD14 (sCD14) levels were measured with an ELISA kit. Results: It was found that CD14+CD16+ monocytes before HD were significantly increased in patients on HD as compared to healthy controls. In the RC group, CD14+CD16+ monocytes were decreased at both 30 and 240 min after the initiation of HD. The reduction rate of CD14+CD16+ monocytes in the RC group was higher than that in the PS group. There was no significant difference in sCD14 levels between the two groups. Conclusion: Monocytes are activated in patients on HD. Furthermore, the population of CD14+CD16+ monocytes was stimulated to a greater extent during HD in the RC group than in the PS group. The significant reduction in CD14+CD16+ monocytes by RC membranes indicated that the level of CD14+CD16+ monocytes is a sensitive marker for the biocompatibility of HD membranes.

“…Several studies have clearly demonstrated the importance of changes in the expression of adhesion molecules on leukocytes in the pathogenesis of dialysis-induced granulocytopenia [3, 4, 5, 6, 7, 8, 9, 10, 11]. …”

Section: Introductionmentioning

confidence: 99%

“…The granulocytopenia and its reversal during hemodialysis with first-use cellulose membrane have been shown to be associated with an upregulation of the integrin receptor Mac-1 expression [3, 4, 5, 6, 7, 8, 9, 10, 11]and downregulation of L-selectin expression on granulocytes [9, 10, 11]. It has been reported that the increased density of Mac-1 on granulocytes, during hemodialysis with first-use cellulose membrane, leads to increased adhesiveness both to other granulocytes and to endothelium, resulting in granulocytopenia [10].…”

Section: Introductionmentioning

confidence: 99%

CD31 Expression on Leukocytes Is Downregulated in vivo during Hemodialysis

Kono

Nakai

Misawa

et al. 2001

Background/Aim: CD31 on leukocytes is the adhesion molecule involved in the leukocyte extravasation in inflammatory conditions. During hemodialysis with cellulosic membranes, it is considered that activated leukocytes adhere to endothelium, but do not show extravasation. However, it is not elucidated why activated leukocytes do not show endothelial transmigration during hemodialysis with cellulosic membranes. Methods: In the present study, changes in the expressions of Mac-1 and CD31 on granulocytes and monocytes were analyzed by flow cytometry during hemodialysis in 7 patients treated with regenerated-cellulose (RC) membranes and next with polysulfone (PS) membranes. Results: During dialysis with RC, Mac-1 expressions on granulocytes and monocytes both significantly increased as compared with predialysis values and across the dialyzer. During dialysis with RC, the CD31 expression on granulocytes and monocytes significantly decreased as compared with predialysis values. During dialysis with PS, changes in Mac-1 and CD31 expressions on granulocytes and monocytes were smaller than those during dialysis with RC. Conclusions: Decreased CD31 expression on leukocytes may affect leukocyte function more in patients chronically hemodialyzed with RC than in those hemodialyzed with PS, since CD31 is important in leukocyte transendothelial migration in inflammatory conditions.