Nobuhito Kashiwagi ¹, Minoru Nakano, Abby R Saniabadi, Masakazu Adachi, Toshikazu Yoshikawa

Inflammation 2002 Aug;26(4):199-205. doi: 10.1023/a:1016523914161.

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.

https://pubmed.ncbi.nlm.nih.gov/12184634/

Toshio Shinoda, September 2002Therapeutic Apheresis and Dialysis 6(4):245-6.

https://www.researchgate.net/publication/11221662_Photopheresis_and_Leukocytapheresis_Cytapheresis_Treatment_Against_Immune-Mediated_Diseases

M Kyogoku ¹, R Kasukawa, Inflamm Res. 1998 Oct;47 Suppl 3:S166-76.

 The results were further confirmed in the adjuvant arthritic rat model. G-1 beads adsorb some amounts of platelets at the beginning and then about a quarter of circulating neutrophils, monocytes, natural killer cells, and B cells, but not T cells. Various factors released from blood cells during transit through the column must have influenced the cells including lymphocytes which passed through the column. G-column actually eliminates some parts of aggressive leukocytes, but a more interesting story is the modification of blood components, which occurred in the G-1 column, and when returned to the patients, may have ameliorated the unbalanced homeostatic network and induced acceleration of healing

https://pubmed.ncbi.nlm.nih.gov/9831320/

N Kashiwagi ¹, I Hirata, R Kasukawa

Ther Apher. 1998 May;2(2):134-41. doi: 10.1111/j.1744-9987.1998.tb00091.x.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.

https://pubmed.ncbi.nlm.nih.gov/10225715/

M Nagashima ¹, S Yoshino, H Tanaka, N Yoshida, N Kashiwagi, A R Saniabadi

Rheumatol Int. 1998;18(3):113-8. doi: 10.1007/s002960050068.

To investigate if granulocyte and monocyte apheresis mitigates the symptoms of rheumatoid arthritis (RA), and influences production of panmyelocytes (CD15+ CD16- cells) at the bone marrow level, 27 RA patients who had elevated granulocyte counts were recruited. The granulocyte and monocyte apheresis column (G-1 column) is an extracorporeal type device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. Patients received apheresis of 1 hr duration twice per week, 8 times over a period of 4 weeks. To prepare CD15+CD16- cells, iliac bone marrow aspirate was obtained at baseline and at 2 weeks after completion of the apheresis course. Ex-vivo proliferation of bone marrow low density cells and production of IgM-RF were also investigated. Following granulocyte and monocyte apheresis, there was a suppressed tendency in the number of CD15+CD16- cells in patients with high bone marrow CD15+CD16- cell counts at baseline. Clinical assessments 2 weeks after the completion of apheresis therapy showed improvements in swollen joint count (P < 0.001), tender joint count (P < 0.001) and duration of morning stiffness (P < 0.005). The results suggest that granulocytes and monocytes/macrophages have a pathological role in RA and apheresis treatment to reduce or suppress these cells should benefit patients with RA.

https://pubmed.ncbi.nlm.nih.gov/9833252/

https://link.springer.com/article/10.1007%2Fs002960050068

Shigebumi Tanaka, Nobuhito Kashiwagi, Masakazu Adachi, Takayuki Asao, Yukio Nagamachi, https://doi.org/10.2974/kmj.47.393

These findings suggest that the G-1 column might suppress lung injury and improve the survival in endotoxin shock model by eliminating the activated granulocytes. Thus, the G-1 column may be useful in endotoxin shock therapy.

https://www.jstage.jst.go.jp/article/kmj1997/47/6/47_6_393/_article

https://www.jstage.jst.go.jp/article/kmj1997/47/6/47_6_393/_pdf/-char/en

C D’Arrigo ¹, J J Candal-Couto, M Greer, D J Veale, J M Woof Clin Exp Immunol 1995 Apr;100(1):173-9. doi: 10.1111/j.1365-2249.1995.tb03620.x.

Human polymorphonuclear cells (PMN) were found to adhere to a novel model of blood vessel wall-associated IgG. The internal surfaces of cellulose acetate hollow fibres, of comparable internal diameter to small blood vessels, were coated with normal serum human IgG, heat-aggregated IgG (HAIgG), laminin or fibrinogen. Under conditions of flow mimicking those in a small vessel, PMN were found to adhere markedly only to immunoglobulin-coated fibres. Arrest on HAIgG was inhibited by excess soluble IgG but not by bovine serum albumin (BSA), demonstrating that the adhesion was IgG-specific and presumably mediated by Fc gamma R on the PMN surface. Pre-adsorption of serum components onto HAIgG-coated fibres enhanced PMN arrest, due most probably to fixation of complement components by immobilized HAIgG, resulting in additional potential to entrap PMN via complement receptors such as CR3. Treatment of PMN with the regulatory neuropeptide substance P also enhanced adhesion to HAIgG-coated fibres and caused increased surface expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII. A mouse cell line derived from L cells, hR4C6, stably transfected with human Fc gamma RII, was found to adhere under flow to HAIgG-coated fibres, whilst untransfected parent L cells did not. This adhesion was similarly inhibited by excess soluble IgG, confirming the capability of Fc gamma R to mediate cell arrest. The study strongly suggests that Fc gamma R may play an important role in intravascular PMN arrest and we speculate that in inflammatory diseases PMN may adhere via Fc gamma R to immobilized immunoglobulin on the vascular endothelium, with subsequent degranulation and tissue damage.

https://pubmed.ncbi.nlm.nih.gov/7535210/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534271/