Monocyte-Related Determinants of Inflammation in Patients on Peritoneal Dialysis

Abstract

Aims: We studied markers of monocyte activation, i.e., the cell surface expression of CD11b and CD62L, and the serum concentrations of monocyte chemotactic protein 1 (MCP-1; a monocyte-specific chemoattractant) and soluble vascular cell adhesion molecule 1 (sVCAM-1; an adhesion molecule involved in monocyte recruitment) in 20 patients on peritoneal dialysis (PD), in 25 patients with chronic renal insufficiency, and in 27 healthy subjects. Results: Monocytes obtained from the peripheral blood of PD patients had a significantly higher expression of CD62L (p = 0.02) as compared with monocytes from healthy subjects and a lower CD11b/CD18 expression as compared with monocytes collected from healthy subjects (p < 0.001) and from patients with renal insufficiency (p < 0.001). Monocytes from PD patients had, however, the capacity to increase the expression of CD11b following stimulation with a potent chemotactic factor. The serum concentrations of MCP-1 and sVCAM-1 were higher in PD patients (575 ± 51 and 1,517 ± 89 ng/ml) than in healthy subjects (225 ± 17 and 668 ± 64 ng/ml, respectively; p < 0.001 for both comparisons). There was a correlation between the levels of sVCAM-1 and MCP-1 (r = 0.48, p < 0.05) in patients on PD, but neither correlated with the monocyte expression of CD11b/CD18 or CD62L. The concentration of C-reactive protein was higher in patients on PD as compared with healthy subjects and correlated significantly with the concentration of sVCAM-1 (r = 0.63, p < 0.01). Conclusions: Monocytes in the peripheral circulation of patients on PD have a CD62L^high/CD11b^low phenotype, indicating that they have not undergone complete differentiation. Patients also have an increase in the systemic chemotactic activity for monocytes in combination with increased levels of sVCAM-1 and C-reactive protein. These inflammatory aberrations may play a pathophysiological role in the response to inflammatory and infectious diseases in patients on PD.

Profound Mishandling of Protein Glycation Degradation Products in Uremia and Dialysis

“…The plasma concentration of MCP-1 was increased significantly in PD and HD patients, and the plasma concentration of soluble TGF-␤ was increased in HD patients only, confirming previous reports (33)(34)(35)(36). MCP-1 is associated with macrophage infiltration into the peritoneal cavity of PD patients and correlates with soluble adhesion molecule expression in HD (33,37).…”

Correlation between Soluble Markers of Endothelial Dysfunction in Patients with Renal Failure

“…As reported earlier [20,21], the concentration of sVCAM-1 was significantly higher in patients with kidney diseases as compared to healthy subjects.…”

“…Informed consent was obtained and the study was approved by the Ethics Committee of the Karolinska Hospital. Most of the patients participating in this study have been described in two recent studies [20,21].…”

“…This procedure has been described in detail recently [20,21]. Briefly, blood samples were collected in EDTA-tubes, hemolysed in 100-Ìl portions, incubated at +4°C for 5 min and then centrifuged at 300 g for 5 min at +4°C.…”

Forkhead Box M1 Transcription Factor Is Required for Macrophage Recruitment during Liver Repair

“…Published studies demonstrated that activated monocytes increased cell surface expression of CD62L (L-selectin) prior to their migration into injured tissues (11,25). Therefore, we used flow cytometry to examine CD62L expression on monocytes during liver injury (Fig.…”