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Titolo:
Parenteral administration of an activating monoclonal antibody to the alpha 1 beta 1 integrin in dogs
Autore:
Bank, I; Hardan, I; Lokshin, E; Nas, D; Miron, S; Ohad, D; Spong, S; Garrod, DR;
Indirizzi:
Chaim Sheba Med Ctr, Dept Med F, IL-52621 Tel Hashomer, Israel Chaim ShebaMed Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Immunoregulat Lab, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Inst Hematol, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Dept Pathol, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Neuroimmunol Unit, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Neufeld Cardiac Res Inst, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 ac Med, IL-69978 Tel Aviv, Israel Univ Manchester, Sch Biol Sci, Manchester, Lancs, England Univ ManchesterManchester Lancs England Sci, Manchester, Lancs, England
Titolo Testata:
IMMUNOBIOLOGY
fascicolo: 3, volume: 202, anno: 2000,
pagine: 239 - 253
SICI:
0171-2985(200009)202:3<239:PAOAAM>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELLS; MYCOSIS-FUNGOIDES; COLLAGEN RECEPTOR; PRIMARY CULTURE; LYMPHOCYTES-T; IN-VIVO; VLA-1; EXPRESSION; ANTIGEN; LAMININ;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Bank, I Chaim Sheba Med Ctr, Dept Med F, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 ashomer, Israel
Citazione:
I. Bank et al., "Parenteral administration of an activating monoclonal antibody to the alpha 1 beta 1 integrin in dogs", IMMUNOBIOL, 202(3), 2000, pp. 239-253

Abstract

In mice, monoclonal antibody (mAb) to the alpha 1 integrin abrogate gastro-intestinal damage during graft-versus-host-disease (GVHD), suggesting antialpha 1 mAb as candidates for treatment in humans as well. Our current data show that one such reagent, mAb 1B3.1, when immobilized to plastic wells via rabbit- anti murine (ram) immunoglobulin (Ig) induces a protein kinase-dependent spreading of activated human T cells. Furthermore, it significantly increases the proliferative response, and expression of interleukin-2 (IL-2) receptors (R) and CD69, of resting T cells, expressing minimal integrin on the cell surface, to sub-optimal stimulation by anti-CD3 mAb. We found, in addition, that mAb 1B3.1 a) immune-precipitates alpha 1 beta 1 integrins from cell-surface iodinated canine epithelial cells b) is highly reactive with canine T cells after their activation and c) inhibits adhesion of canine T cells to collagen IV Despite the potential ability of the mAb to co-activate T cells in vitro, two dogs that received 4 injections of 0.5-0.3 mg/Kg of mAb 1B3.1 remained healthy, developing only marginal transient lymphopenia. Injection of 0.75mg/Kg in a third dog induced a more marked lymphopenia, and an additional dose of 1.0 mg/Kg 2 weeks later was followed by gastrointestinal hemorrhage. Importantly, the lymphopenia was associated witha greater and more persistent decrease of CD8(+) than of CD4(+) T cells, leading to an increase in the CD4/CD8 ratio 24 hours after the injection. Thus, despite it's co-activating effects in vitro, administration of this mAbin viva is feasible when appropriately dosed, and may have immuno-modulatory effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 01:15:10