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Biomedical subjects

L B Epstein

Publications and source records attributed to L B Epstein.

86 records · Page 5Linked to original sources
PubMed1972

Selective increase in lymphocyte interferon response to vaccinia antigen after revaccination.

Viral antigen prepared by heat inactivation of vaccinia virus stimulated production of interferon in association with transformation of sensitized human lymphocytes in vitro. Involvement of a macrophage-lymphocyte interaction in production of interferon stimulated by viral antigen was found in which macrophage greatly augmented the amount of interferon produced by lymphocytes. Reimmunization with live vaccinia virus resulted in a selective increase in the ability of lymphocytes to produce interferon in the presence of viral antigen 4-7 weeks later without a corresponding increase in the degree of already significant lymphocyte transformation. There was no correlation between the extent of lymphocyte transformation and the amount of interferon produced. The augmented interferon response after reimmunization described in this study may be a significant component of the protective effect of immunization with vaccinia against disease occurring after exposure to small-pox.

Adult↗
PubMed1971

The interaction of human macrophages and lymphocytes in the phytohemagglutinin-stimulated production of interferon.

In studies of 13 normal adults to determine the blood cell types responsible for interferon production induced by phytohemagglutinin, the following observations were made. (a) In cultures containing 96-100% pure macrophages derived from blood monocytes, no interferon was detected in either the presence or the absence of phytohemagglutinin for up to 92 hr. (b) In cultures of 99.5-100% pure lymphocytes, low levels of interferon were detected in the presence, but not in the absence, of phytohemagglutinin. (c) An average fivefold increase in interferon titers occurred when pure lymphocytes were combined with the macrophages in culture with phytohemagglutinin. The peak response of interferon occurred at 68 hr after the initiation of the combined cultures. For maximum response, phytohemagglutinin was required for the duration of the culture, and both cell types in association were necessary. Medium from phytohemagglutinin-stimulated macrophages or lymphocytes could not substitute for the corresponding intact cell. However, frozen-thawed macrophages in combination with lymphocytes and phytohemagglutinin produced an intermediate interferon response. An increase in either cell type produced an increased response in the range studied: lymphocytes, 0.45-1.8 x 10(6) per ml; and macrophages, 0.5-2.1 x 10(5) per ml. Syngeneic fibroblasts, HeLa cells, or mouse macrophages could not substitute for the human macrophages in the combined cultures with phytohemagglutinin. (d) Although all cultures producing interferon showed some degree of transformation (thymidine-(3)H incorporation into deoxyribonucleic acid), no direct correlation between the degree of phytohemagglutinin-induced lymphocyte transformation and the interferon titers was observed.The demonstration of macrophage-lymphocyte interaction in the production of interferon is of interest in view of the known interrelationship of these same cell types in antibody synthesis and cellular immunity.

Journal Article↗
PubMedDate not supplied

Immobilized pH gradient two-dimensional gel electrophoresis and mass spectrometric identification of cytokine-regulated proteins in ME-180 cervical carcinoma cells.

Two-dimensional (2-D) polyacrylamide gel electrophoresis combined with mass spectrometry is a powerful combination of technologies that allows high resolution separation of proteins and their rapid identification. Immobilized pH gradient (IPG) first-dimensional gels have several advantages over carrier ampholyte isoelectric focusing, including a high degree of reproducibility, good protein spot resolution, and a selection of pH range. Here we demonstrate the utility and efficacy of combining IPG 2-D gel electrophoresis with mass spectrometry to identify interferon-gamma- (IFN) and tumor necrosis factor (TNF)-regulated proteins in ME-180 cervical carcinoma cells. Three cytokine-regulated proteins have been identified, using imidazole-zinc-stained preparative IPG 2-D gels and in-gel tryptic digestion followed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for determination of peptide masses and sequences: 1) triosephosphate isomerase, a glycolytic pathway enzyme, 2) proteasome subunit C3, which is important in protein degradation, and 3) Ran, a GTP-binding protein important in cell cycle regulation, protein import into the nucleus, and RNA export from the nucleus.

Amino Acid Sequence↗
PubMedDate not supplied

Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1.

Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cells in vitro and thus represent an important component of the host defence mechanisms against malignancy. The recent availability of pure recombinant or natural human lymphokines and monokines and their respective polyclonal or monoclonal antibodies now makes it possible to dissect the interactions of these factors in the induction and performance of the cytotoxic event by the monocytes. Our studies indicate that pretreatment of monocytes with alpha-IFN or gamma-IFN, and also interleukin (IL)-1 or tumour necrosis factor (TNF) results in enhanced monocyte cytotoxicity. Although all these substances induce the production of IL-1 by monocytes, TNF mediates the enhanced cytotoxicity induced in monocytes by gamma-IFN, IL-1 and, in an autocrine manner, by TNF itself. Neither TNF, IL-1, gamma-IFN nor alpha-IFN mediate spontaneous monocyte cytotoxicity or that induced by alpha-IFN. Our studies thus reveal new interactions between the two monokines IL-1 and TNF and provide a dual role for TNF, as immunomodulator and mediator of monocyte cytotoxicity induced by certain specific lymphokine and monokine molecules.

Animals↗
PubMedDate not supplied

Polypeptide induction by recombinant human IFN-gamma.

Partially purified natural human IFN-gamma has been shown to induce the synthesis of a set of unique polypeptides that are not induced by comparable amounts of IFN-alpha and IFN-beta. In addition, a set of polypeptides is induced in common by all three IFNs. The present study utilized a pure recombinant IFN-gamma and a monoclonal antibody against IFN-gamma to investigate whether the unique polypeptide-inducing properties previously reported are due to IFN-gamma itself. With the possible exception of two polypeptides, the results demonstrate conclusively that IFN-gamma is the sole molecular species responsible for the induction of all polypeptides, including those whose induction pattern is unique to IFN-gamma. Very high doses of IFN-alpha and IFN-beta induce some of the latter set of polypeptides to a limited extent. Thus the differential effects of IFN-gamma compared to IFN-alpha and IFN-beta are, in part, quantitative rather than qualitative in nature.

Antibodies, Monoclonal↗
PubMedDate not supplied

Characterization of TNF receptors on human thymocytes.

Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation and survival suggest that its influence in the thymus is complex. To determine if this complexity results from changes in the expression of the two TNF receptors during thymocyte differentiation, we examined the expression of the 55 kDa TNF receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which specifically react with the respective TNF receptors and a highly sensitive, three-step method of immunofluorescence, cell surface TNF-R1 was detected on the vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin (TNF-PE) also reacted with a small population of thymocytes and was found to specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence with TNF-PE we found that the population of cells which express TNF-R2 also express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2 receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression of TNF receptors provides a mechanism for distinct effects of TNF on immature vs. mature thymocytes.

Animals↗