title: Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis.
abstract: 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.
authors.affiliation: Japan Immunoresearch Laboratories, Takasaki, Gunma, Japan. hiraishik@jimro.co.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hiraishi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takeda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shiobara
authors.forename: Hiromu
authors.initials: H
authors.lastname: Shibusawa
authors.forename: Fumie
authors.initials: F
authors.lastname: Jimma
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Kashiwagi
authors.forename: Abby R
authors.initials: AR
authors.lastname: Saniabadi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Adachi
mesh_terms: D001781:Blood Component Removal / Q000295:instrumentation / Q000379:methods*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D011336:Probability; D017452:Receptors, IgG / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012016:Reference Values; D012680:Sensitivity and Specificity; D000267:Tissue Adhesions
chemical_list: D015815:Cell Adhesion Molecules; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; C005062:acetylcellulose; D002482:Cellulose