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Titolo:
EFFECT OF INTERLEUKIN-12 ON ANTITUMOR-ACTIVITY OF HUMAN UMBILICAL-CORD BLOOD AND BONE-MARROW CYTOTOXIC-CELLS
Autore:
CONDIOTTI R; NAGLER A;
Indirizzi:
HADASSAH UNIV HOSP,DEPT BONE MARROW TRANSPLANTAT IL-91120 JERUSALEM ISRAEL HADASSAH UNIV HOSP,DEPT BONE MARROW TRANSPLANTAT IL-91120 JERUSALEM ISRAEL HADASSAH UNIV HOSP,ISRAEL NATL CORD BLOOD BANK IL-91120 JERUSALEM ISRAEL
Titolo Testata:
Experimental hematology
fascicolo: 7, volume: 26, anno: 1998,
pagine: 571 - 579
SICI:
0301-472X(1998)26:7<571:EOIOAO>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
NATURAL-KILLER-CELLS; VERSUS-HOST DISEASE; CHRONIC MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; CHRONIC MYELOGENOUS LEUKEMIA; T-CELL; PERIPHERAL-BLOOD; NK CELL; MEDIATED CYTOTOXICITY; MOLECULAR MECHANISMS;
Keywords:
INTERLEUKIN-12; INTERLEUKIN-2; HUMAN UMBILICAL CORD BLOOD; NATURAL KILLER CELLS; BONE MARROW; NONMAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED CYTOTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
R. Condiotti e A. Nagler, "EFFECT OF INTERLEUKIN-12 ON ANTITUMOR-ACTIVITY OF HUMAN UMBILICAL-CORD BLOOD AND BONE-MARROW CYTOTOXIC-CELLS", Experimental hematology, 26(7), 1998, pp. 571-579

Abstract

Interleukin (IL)-12, a natural killer (NK) cell stimulatory factor, is a heterodimeric cytokine that is known to be a potent activator of non-major histocompatibility complex-restricted cytotoxicity by peripheral blood-derived NK cells. NK cells (CD3(-)CD16(+)/CD56(+)) representapproximately 15% of human umbilical cord blood mononuclear cells (HUCB MNCs) and are known to be highly sensitive to activation by IL-2. In the present study, we monitored the effect of IL-12 on the cytotoxicactivity, proliferation, and phenotypic expression of HUCB-derived resting and IL-2-activated cytotoxic cells and compared these parameterswith those of bone marrow (BM)derived cells. Lymphocytes were separated from HUCB by 3% gelatin sedimentation and incubated with IL-12 and/or IL-2 for 18 hours. At effector:target ratios of 40:1 and 20:1, IL-12 (50 U/mL) significantly increased both resting and IL-2-activated NKcell-mediated cytotoxicity in a standard Cr-51-release assay against both NK-sensitive (K562) and NK-resistant (Colo-205) cell lines. In addition, resting and IL-2-activated cytotoxic cells derived from HUCB exhibited superior cytolytic ability compared with BM-derived cells. This increase was observed in resting cells as well as in those that were preincubated with IL-12. Moreover, HUCB-derived cells were found to be more sensitive to IL-12 activation than cytotoxic cells from BM. Toevaluate the involvement of accessory cells, NK cells were purified from HUCB using immunomagnetic beads, and these cells were found to have a lower response to treatment with IL-12 than unpurified populations. HUCB MNCs exhibited a nonsignificant increase in proliferation afterIL-12 treatment and were better able to respond to IL-12 activation than BM MNCs. Following an 18-hour incubation, IL-12 was able to cause upregulation of CD25 and CD69 activation antigens, whereas no significant change in expression of CD16 and CD56 NK cell surface antigens, CD3 on T cells, or IL-12 receptor was observed. Similarly, IL-12 did notaffect NK cell:target cell conjugation as assessed by fluorescence-activated cell sorting. Our results indicate that HUCB-derived NK-mediated cytotoxic capabilities can be increased by IL-12, a finding that may have clinical relevance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 00:47:04