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C Bordignon

Publications and source records attributed to C Bordignon.

83 records · Page 5Linked to original sources
PubMed1987

Selective expression of fos proto-oncogene in human acute myelomonocytic and monocytic leukemias: a molecular marker of terminal differentiation.

Expression of human fos proto-oncogene (c-fos) was analyzed in primary cells from 50 untreated acute lymphocytic (ALL) and myeloblastic (AML) leukemias. c-fos RNA, analyzed by blot hybridization, was detected virtually only in myelomonocytic (M4) and monocytic (M5) AML. Both M4 and M5 samples show a strong positive correlation between the amount of c-fos transcripts and the percentage of leukemic cells expressing surface antigens specific for mature monocytes and macrophages. Normal mature monocytes exhibit a detectable level of c-fos RNA, which is virtually unaltered on activation to macrophage differentiation, but is always below that observed in M4 through M5 monocyticlike cells. These data provide evidence that c-fos expression is linked to terminal monocyte and macrophage differentiation in normal and leukemic hemopoiesis.

Antigens, Neoplasm↗
PubMed1985

Hematopoietic histoincompatibility reactions by NK cells in vitro: model for genetic resistance to marrow grafts.

In certain strains of mice, bone marrow grafts from parental donors fail to grow in first-generation hybrid mice. This "hybrid resistance" of nonsensitized F1 hybrid mice to the engraftment of parental hematopoietic transplants contradicts the classical laws of transplantation and is dependent on a radioresistant but immunogenetically specific effector mechanism. Studies in a new in vitro model reveal that committed hematopoietic precursors of parental origin can be inactivated by direct contact with natural killer-like splenic effectors from F1 mice. The reaction requires genetically restricted recognition, since only parental competitors syngeneic to the target bone marrow cells partially reversed this inactivation. Models of this type may be useful in studying the possible role of natural resistance in bone marrow transplantation in humans.

Animals↗
PubMed1984

Human mononuclear phagocytes from different anatomical sites differ in their capacity to metabolize arachidonic acid.

Human mononuclear phagocytes have the capacity to metabolize arachidonic acid (AA) into prostaglandins (PG) endowed with potent activities in immune responses and inflammatory processes. We have evaluated AA metabolism in human mononuclear phagocytes harvested from different anatomical sites (blood monocytes, macrophages from milk, peritoneal cavity and alveolar spaces). At thin layer radiochromatography, the AA metabolites mainly present were PGE2, TxB2 and, only in bronchoalveolar macrophages, a peak comigrating with PGD2. No appreciable levels of 6-keto-PGF1 alpha were observed. These data were confirmed using specific radioimmunoassays for TxB2, PGE2 and 6-keto-PGF1 alpha. Blood monocytes and bronchoalveolar macrophages were the poorest producers of PG, with the possible exception of PGD2 in bronchoalveolar macrophages. The high amounts of TxB2 and PGE2 produced by milk macrophages could contribute to the levels of PG in human milk. Thus, human mononuclear phagocytes obtained from diverse anatomical sites are considerably heterogeneous in terms of AA metabolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Natural cytotoxic activity in human lungs.

Disease-free surgical lung specimens from 13 patients with neoplastic or infectious diseases and from three subjects with non-neoplastic, non-infectious pathology were mechanically disaggregated. Natural cytotoxicity was tested against 51Cr-labelled K562 target cells. Unseparated lung cells had little cytotoxicity against K562 cells. Removal of plastic and nylon-wool-adherent cells resulted in cell preparations (morphologically 80% lymphoid) with increased cytolytic activity against K562 but cytotoxicity levels were considerably lower than those of blood lymphocytes tested in parallel. Similar results were obtained when phagocytic adherent cells were removed with carbonyl iron. The NK-resistant murine TU5 and human Raji lines were not affected by lung effector cells. In vitro exposure to partially purified fibroblast interferon enhanced the cytotoxicity of unseparated or non-adherent lung cells. Thus, unlike in mouse pulmonary tissue, low levels of natural cytotoxic activity are associated with the humans lung.

Cell Survival↗
PubMed1982

Inhibition of natural killer activity by human bronchoalveolar macrophages.

Mononuclear phagocytes were isolated by adherence from peripheral blood, peritoneal exudates, early lactation milk, ovarian carcinomatous ascites and bronchoalveolar lavages. Their capacity to modulate natural killer (NK) activity was assessed by mixing them with blood lymphocytes and by measuring lysis of 51Cr-labeled K562 cells. Unlike other mononuclear phagocyte populations, alveolar macrophages caused a marked dose-dependent inhibition of NK activity. Significant inhibition (40%) of the expression of cytotoxicity was evident at a ratio of alveolar macrophages to lymphoid cells of 0.12:1, and more than 80% suppression was usually observed at a ratio of 0.5:1. Blood monocytes, peritoneal and milk macrophages were consistently inactive up to the highest ratio tested, 2:1. Inhibition of the expression of NK activity by alveolar macrophages was observed at lymphocyte to K562 ratios ranging from 6:1 to 100:1 and over a 4 h or 20 h 51Cr release assay. Alveolar macrophages also inhibited interferon-stimulated cytotoxicity. Alveolar macrophages are unique among the mononuclear phagocyte populations studied in their capacity to inhibit the expression of NK activity effectively, and they could play a role in determining the low levels of NK activity associated with human pulmonary tissue.

Ascitic Fluid↗
PubMed1980

Natural cytotoxicity on tumour cells of human macrophages obtained from diverse anatomical sites.

Human mononuclear phagocytes were isolated from peripheral blood, peritoneal exudate and early lactation milk by adherence on microexudate-coated plastic and exposure to ethylene diamine tetracetic acid. Their cytolytic activity was measured as 3H-thymidine release from prelabelled target cells over 48-72 hr and cytostasis was evaluated in a spectrophotometric 72-hr assay. The murine SV40-transformed mKSA-TU5 line and the human E cell line, derived from an ovarian carcinoma, were employed as targets. Peripheral blood monocytes, in vitro-matured monocyte-derived macrophages, peritoneal macrophages and milk macrophages were all significantly cytolytic and cytostatic on these target cells at attacker to target cell ratios ranging from 5:1 to 40:1. When monocytes were cultivated in vitro, no loss of cytocidal capacity occurred over the first 10 days of culture, whereas later on, when epithelioid and giant cells predominate in the cultures, mononuclear phagocytes had little cytotoxic activity. Adherent cells obtained from cord blood or from the peripheral blood of old donors had natural cytotoxicity similar to monocytes obtained from young adult volunteers. Peripheral blood monocytes and peritoneal macrophages showed enhanced cytolytic activity after exposure to partially purified human fibroblast interferon. These experiments suggest that in the human mononuclear phagocyte series cytotoxicity on tumour cells is not restricted to circulating monocytes but is also expressed by macrophages obtained from diverse anatomical sites.

Adult↗
PubMed1980

Cytotoxicity on tumour cells of human mononuclear phagocytes: defective tumoricidal capacity of alveolar macrophages.

Human cells of the monocyte-macrophage lineage were isolated by adherence from peripheral blood, peritoneal exudate, non-neoplastic ascites, benign ovarian cystic fluid and bronchoalveolar lavages. Cytolytic activity was measured as 3H-thymidine release from prelabelled mKSA TU5 tumour cells over 48-72 hr and cytostasis was evaluated in a 72-hr spectrophotometric assay. Mononuclear phagocytes from the various anatomical sites examined, except lung alveolar spaces, were significantly cytolytic and cytostatic on target cells. Unlike other cells of the monocyte-macrophage lineage, alveolar macrophages were not cytocidal, but significantly inhibited tumour cell proliferative capacity. Peripheral blood monocytes and peritoneal macrophages showed enhanced cytotoxicity in the presence of partially purified human fibroblast interferon or of lymphokine supernatants from mitogen-stimulated lymphocytes. In contrast, interferon did not affect the cytotoxic potential of alveolar macrophages, whereas lymphokines augmented their cytostatic activity and rendered them weakly cytolytic.

Adult↗
PubMedDate not supplied

Optimisation of retroviral supernatant production conditions for the genetic modification of human CD34+ cells.

BACKGROUND: Clinically applicable protocols for ex vivo modification of human CD34+ hematopoietic stem/progenitor cells rely on incubation of the target cell with supernatant containing recombinant retroviral particles. Although components of the supernatant may have a profound impact on both preclinical and clinical outcome, to date supernatant production has not been properly addressed with regard to CD34+ cells. We wanted to investigate and optimise production conditions for this target using simple, reproducible and clinically applicable procedures and reagents. METHODS: Retroviral supernatant was obtained from producer cell GP+Am12 under various production conditions and tested for bulk transduction efficiency and endpoint titre on murine and human cell lines. Gene transfer efficiency into CD34+ cells from mobilised peripheral blood, after a single exposure to retroviral supernatant, was measured by transgene expression, colony forming assay and long-term culture colony forming assay. RESULTS: Bulk gene transfer or endpoint titre values obtained on cell lines for the different production conditions were not predictive of gene transfer efficiency into hematopoietic progenitors. Time of virus production appeared to have the greatest impact on gene transfer, peaking at 6 h and decreasing 2-3-fold at longer time points. Neither the culture vessel used nor the temperature for virus production had any significant effect on gene transfer into CD34+ cells. Supernatant could be produced under defined serum-free conditions as efficiently as serum containing conditions for CD34+ cell gene transfer. CONCLUSIONS: The present data provide important implications for the establishment of quality controls for small- and large-scale clinical grade supernatant production for gene transfer into human hematopoietic stem/progenitor cells.

3T3 Cells↗