Proteomic profiling of blood-dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis-induced inflammatory response

• Published in: Proteomics. Clinical applications Vol. 4; no. 10-11; pp. 829 - 838
• Main Authors: Mares, Jan, Richtrova, Pavlina, Hricinova, Alena, Tuma, Zdenek, Moravec, Jiri, Lysak, Daniel, Matejovic, Martin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.11.2010; WILEY‐VCH Verlag; Wiley
• Subjects: Adsorption; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Complement; Complement Pathway, Mannose-Binding Lectin; Diverse techniques; Emergency and intensive care: renal failure. Dialysis management; Ficolins; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Hemodialysis; Humans; Inflammation; Inflammation - immunology; Inflammation - metabolism; Intensive care medicine; Lectin; Lectins - chemistry; Lectins - metabolism; Leukopenia; Medical sciences; Membranes, Artificial; Molecular and cellular biology; Polymers - chemistry; Polymers - metabolism; Polysulfone; Proteome - analysis; Renal Dialysis - instrumentation; Renal Dialysis - methods; Sulfones - chemistry; Sulfones - metabolism; Lectin; Leukopenia; Hemodialysis; Interactome; Proteomics; Complement; Inflammation; Polysulfone; Blood
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.201000031

Purpose: Dialysis‐induced inflammatory response including leukocyte and complement activation is considered a significant cofactor of chronic morbidity in long‐term hemodialysis (HD) patients. The aim of this study was to provide better insight into its molecular background. Experimental design: In 16 patients, basic biocompatibility markers, i.e. leukocyte counts and C5a levels, were monitored during HD on a polysulfone membrane. Proteins adsorbed to dialyzers were eluted and separated by 2‐DE. Selected proteins were identified by MS; ficolin‐2 plasma levels were assessed. Data are given as medians (quartile ranges). Results: In total, 7.2 (34.7) mg proteins were retrieved from dialyzer eluates and were resolved into 217 protein spots. The proteins most enriched in eluates (and hence selectively adsorbed) were those involved in complement activation (C3c, ficolin‐2, mannan‐binding lectin serine proteases, properdin) and cell adhesion (actin, caldesmon, tropomyosin, vitronectin, vinculin). A significant decrease of plasma ficolin‐2 (41% [4.7], p<0.001) was evidenced during one HD session, associated with leukopenia (r=0.73, p=0.001) and C5a production (r=−0.62, p=0.01) at 15 min. Conclusions and clinical relevance: Ficolin‐2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis‐induced leukopenia, and results in a significant depletion of ficolin‐2, an essential component of innate immunity.