INDUCTION AND AUGMENTATION OF MITOGEN-INDUCED LYMPHOKINE PRODUCTION IN HUMAN PBL BY Nα-Desacetylthymosin Α1

Svedersky, L P; Hui, Anna; G, Don; Wheeler, David; McKay, Patrick Zweider; May, Laurie; Stebbing, Nowell

doi:10.1016/b978-0-12-406080-7.50016-3

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Similar results were obtained for recombinant and purified IL-2 which, according to Svedersky et a!. (12) have similar biological properties, Cotran et ai (13) have recently indicated that intravenous administration of IL-2 leads directly to endothelial cell activation by inducing the production of other cytokinessuch as lL-1. TNFand IFN.…”

Section: Discussionsupporting

confidence: 71%

Response of microvascular endothelial cells to biological response modifiers

1989

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Summary This study investigated in vitro biological response modifiers (BRM) possibly involved in initiation and regulation of human capillary endothelial cell (HCEC) growth. An indicator assay was developed using tritiated thymidine to measure increased DNA turnover. Purified or recombinant BRMs tested singly and in combination included: interferon (IFN; α and γ), tumour necrosis factor (TNF; α and β), transforming growth factor (TGF: α and β). rIL‐1, rIL‐2, pIL‐2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rlL‐2 (≥ 10 U/mL) caused proliferation of the cells. γIFN together with TNFα(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: α or γ IFN (≥ 1000 U/mL), TGFβ (≥5 ng/mL), rIL‐1 (≥ 0·5 U/mL) and rIL‐1 plus γIFN, γIFN (500 U/mL) plus TNFα exhibited synergism in the Inhibition of proliferation and produced a cytotoxic effect at TNFα concentrations ≥500 U/mL. By contrast, rIL‐2 enhanced proliferation at >5 U/mL. When rIL‐2 was combined with γIFN, an inhibitory effect on proliferation was observed, although to a lesser extent than γIFN alone. Pretreating the cells with 100 U/mL γIFN prior to rIL‐1 or IL‐2 exposure produced no change in the trends observed above. TGFα also stimulated cell proliferation at concentrations ≥0·5 ng/mL. PDGF and retinoic acid had no effect on proliferation in the concentration range 0·5‐10 U/mL. By investigating the response of HCEC to these BRMs, the nature of, and response to the signals from immune cells in inflammatory disease processes can be better understood.

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Section: Discussionsupporting

confidence: 71%

Response of microvascular endothelial cells to biological response modifiers

1989

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“…IFN-y is a strong activator of macrophages [22]. This apparently contradicts our observation of the inhibition of macrophage spreading.…”

Section: Discussioncontrasting

confidence: 89%

Production of Gamma Interferon in Mls Disparate Interactions

1988

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The murine T-cell clone E11 isolated from a primary H-2k histocompatible one-way mixed lymphocyte culture of B10.BR anti C3H/Tif spleen cells was used to study multidirectional interactions in strong stimulatory Mls disparate responses. Several parameters have recently been studied, and proliferation of T cells upon stimulation by macrophages or B cells of Mls-disparate stimulator cells, induction of differentiation of B cells of stimulator strains but inhibition of their macrophage differentiation, and the inhibition by E11 T cells of the production of a mitogenic mediator by Mls-disparate spleen cells have been found. As shown in this paper, these phenomena can be explained by an Mlsa, d, e specific induction of gamma-interferon (IFN-gamma) production in the responder B10.BR (Mlsb) E11 T cells. It is suggested that IFN-gamma, as a regulator of feedback mechanisms plays a critical role in Mls disparate T-cell stimulation.

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“…IFN titers were determined by the inhibition of cytopathic effect in microtiter assays (26). The human IFN-/3 assay used encephalomyocarditis virus (EMC) and A549 cells.…”

Section: Methodsmentioning

confidence: 99%

Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor.

Svedersky¹,

Benton²,

Berger³

et al. 1984

The Journal of Experimental Medicine

113

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The multiple biological activities present in semipurified lymphokine preparations have made it difficult to assign discrete biological functions to each lymphokine. As a result, the large number of identified lymphokine activities may actually reflect the manifestations of a few factors. While this research has also been hampered by the limited quantities of lymphokines available, hybridoma and recombinant DNA technologies have begun to help overcome these limitations.Macrophage activation has been intensively investigated because it is generally agreed that activated macrophages play an essential role in the defense against microorganisms and in the immune response against neoplasia (1). Macrophage activation mediated by macrophage activation factor (MAF) 1 and gamma interferon (IFN-'y) has been characterized by similar morphologic, metabolic, and functional changes (2-6) including stimulation of nonspecific tumoricidal activities (5), induction of Ia antigen expression (7, 8), increased Fc receptor expression (0, 10), production of plasminogen activator (I 1), and production of hydrogen peroxide (12). Several investigators (5,8,12,13) have postulated therefore that IFN-q~ and MAF may be identical. In support, Schreiber et al. (14) have recently demonstrated biosynthetic and biochemical similarities of IFN-'y and MAF produced by a murine T cell hybridoma (24/G1). Both the antiviral and MAF activities of 24/G1 cultured supernatants were neutralized by anti-IFN-% but not anti- . have demonstrated neutralization of MAF activity with polyclonal antMFN-7, definitive results could not be ascertained since these antisera were prepared from partially purified preparations and could contain antibodies that neutralize other lymphokine activities.In the present report, murine IFN-~ produced by recombinant DNA techniques (18) (>00% pure) was tested for MAF activity; special attention was given

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INDUCTION AND AUGMENTATION OF MITOGEN-INDUCED LYMPHOKINE PRODUCTION IN HUMAN PBL BY Nα-Desacetylthymosin Α1

Cited by 4 publications

References 10 publications

Response of microvascular endothelial cells to biological response modifiers

Response of microvascular endothelial cells to biological response modifiers

Production of Gamma Interferon in Mls Disparate Interactions

Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor.

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