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


METHODS
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
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.
Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, Plzen, Czech Republic. mares@fnplzen.cz
Jan
J
Mares
Pavlina
P
Richtrova
Alena
A
Hricinova
Zdenek
Z
Tuma
Jiri
J
Moravec
Daniel
D
Lysak
Martin
M
Matejovic
D000327:Adsorption; D037582:Complement Pathway, Mannose-Binding Lectin; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D013450:Sulfones / Q000737:chemistry / Q000378:metabolism; D000097604:Ficolins
D037102:Lectins; D008567:Membranes, Artificial; D011108:Polymers; D020543:Proteome; D013450:Sulfones; D000097604:Ficolins; C017662:polysulfone P 1700