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Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37 degrees C for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes. CD19+ (B cells) and CD56+ (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16- granulocytes and CD14+ monocytes, but not on CD3+ lymphocytes In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.

In active rheumatoid arthritis, large numbers of granulocytes and macrophages are found in the inflamed joints. These leucocytes can promote inflammation and tissue injury by releasing inflammatory cytokines, proteinases and oxygen derivatives. To see if granulocyte and monocyte (GM) depletion produces anti-inflammatory effect, GM adsorption apheresis was performed in rabbits with immune arthritis by using a column (Adacolumn) filled with cellulose diacetate beads (G-1 beads) as adsorptive carriers which selectively adsorb CD11b positive GMs. Injection of ovalbumin into the knee joints of ovalbumin-sensitized rabbits caused a marked increase in peripheral blood leucocytes, joint swelling, increased granulocyte adhesion to G-1 beads and elevated TNF-alpha production by peripheral blood mononuclear cells (PBMC). When rabbits received a 60 min adsorption apheresis, there was suppression of CD11b positive leucocyte infiltration into the joint and reduced joint swelling (P < 0.01) compared with controls. Additionally, there was a significant (p < 0.01) suppression of TNF-alpha production by PBMC in the post column blood. These results suggest that GM depletion may serve as a non-pharmacological strategy to modify inflammatory disorders.

Examines the effectivity of granulocytapheresis in treating cancer. Influence of granulocytes in tumor growth; Complications caused by the use of granulocytapheresis; Advantages of granulocytapheresis over other cancer treatments.