Cell apoptosis and hemodialysis-induced inflammation.
Hemodialysis patients exhibit a defective immune response leading to an increased susceptibility of infections and neoplasms. Far from being helpful, dialytic therapy per se also may be responsible for this acquired immunodeficiency. Dialysis membranes and bacterial products present in dialysis water may trigger and even perpetuate an abnormal mononuclear cell activation. Upon contact with cellulosic dialysis membranes, monocytes display an increased expression of surface markers of cell activation, such as adhesion molecules CD18, CD49, CD54 and the lipopolysaccharide (LPS) ligand (CD14). Moreover, proinflammatory cytokines as IL-1beta and TNF-alpha are released both in vivo and in vitro when monocytes are exposed to cellulosic membranes. Of special interest is the fact that end-stage renal disease patients undergoing hemodialysis exhibit an increased mononuclear cell apoptosis. This apoptosis is directly related to the degree of biocompatibility of the dialysis membrane. Apoptosis is activated when monocytes enter in contact with the cellulosic dialysis membrane through cell surface receptors linked to G-proteins. In early steps of apoptosis signaling, pertussis toxin-sensitive G proteins are coupled to protein kinase C (PKC)-dependent phosphorylative mechanisms. Furthermore, recent evidence support that the execution phase of apoptosis is mediated by a caspase-3 dependent pathway. Finally, very recent available data support that monocytes subjected to repeated activation suffer a process of accelerated senescence, as demonstrated by the senescent phenotype (CD14 and CD32) expressed and their shortened telomeric length. This senescent profile may generage a defective cellular response in acute stress situations, explaining (at least in part) the altered immune response observed in hemodialysis patients.
Carracedo
Julia
J
Servicio de Nefrología, Unidad de Investigación, Hospital Universitario, Reina Sofía, Córdoba, Spain.
Ramírez
Rafael
R
Madueño
Juan A
JA
Soriano
Sagrario
S
Rodríguez-Benot
Alberto
A
Rodríguez
Mariano
M
Martín-Malo
Alejandro
A
Aljama
Pedro
P
D000210:Acute-Phase Reaction / Q000209:etiology* / Q000473:pathology*; D017209:Apoptosis; D002482:Cellulose; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008567:Membranes, Artificial; D006435:Renal Dialysis / Q000009:adverse effects*
D008567:Membranes, Artificial; D002482:Cellulose