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Biomedical subjects

S M Hsu

Publications and source records attributed to S M Hsu.

At least 91 records · Page 5Linked to original sources
PubMed1989

Aberrant expression of T cell and B cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells. Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin for Hodgkin's Reed-Sternberg cells?

Most Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells are characterized by the expression of the antigen CD30, but not of T or B cell markers. A few H-RS cells, however, may express a limited number of T or B cell markers. Whether this expression is sufficient to allow the conclusion that H-RS cells are derived from T and/or B cells has been debated vigorously. The present study examined whether CD30 and aberrant T and B cell markers are expressed in cell lines that are well documented as being derived from the granulocyte/monocyte/histiocyte lineage. These cells included HL-60, KG-1, ML-1, THP-1, and U-937. Four other cell lines derived from patients with leukemias/lymphomas of monocytic or granulocytic origins also were studied. These cells included BV173, CML-Brown, CTV-2, and SU-DHL-1. If aberrant expression is detected, by analogy one may expect that rare T or B cell marker expression may occur in H-RS cells, because abundant evidence has indicated that H-RS cells may be related to cells in histiocyte lineage. In all nine of the cell lines studied, it was confirmed that numerous monocyte/granulocyte markers were expressed. The marker expression was enhanced after cells were induced to differentiate with phorbol ester (TPA) and tumor necrosis factor (TNF). It was noted that several T and B cell markers also were expressed by these cells. Unlike the expression of monocyte/granulocyte markers, the expression of T or B cell markers was not affected, or only minimally affected, by treatment of the cells with TPA or TNF. Five of the cell lines (BV173, CML-Brown, CTV-2, SU-DHL-1, and THP-1) were shown to be CD30-positive. In CTV-2 and BV173, the expression of CD30 was greatly increased after induction with phorbol ester or TNF. Based on these studies, the following conclusions were reached: 1) The expression of aberrant B or T cell markers is not an uncommon finding in granulocyte/monocyte/histiocyte-related neoplastic cells. 2) The expression of granulocyte/monocyte markers in these cells is related to the state of cell differentiation, whereas the expression of T or B cell markers is not. 3) CD30 is not necessarily a proliferation-related antigen, and its expression is not a sole property of T or B cells, but can be present in granulocyte/monocyte/histiocyte-related cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Heterogeneity of interleukin 1 production in cultured Reed-Sternberg cell lines HDLM-1, HDLM-1d, and KM-H2.

Interleukin 1 (IL-1) is known for its role in modulating the immune response and is required for initiation of lymphocyte proliferation by means of increased IL-2 production by lymphocytes. Previously, the expression of IL-1 in H-RS cells in tissue sections was shown by using immunoperoxidase staining. For further confirmation, the production of IL-1 in cultured cells of the H-RS cell lines HDLM-1, HDLM-1d, and KM-H2 was examined by using a murine D10.G4.1 T cell proliferation bioassay and Northern blot hybridization with specific IL-1 cDNA probes. It was confirmed that two types of H-RS cells, HDLM-1 and KM-H2, can secrete IL-1, especially after treatment with phorbol ester. The amounts of IL-1 in H-RS cell culture medium ranged from approximately 0.5 to 2.5 ng/ml. The major IL-1 secreted by HDLM-1 cells was IL-1 alpha, and by KM-H2 cells was IL-1 beta. HDLM-1d cells did not produce IL-1. This finding indicates the heterogeneity of IL-1 production in H-RS cells. Such heterogeneity may apply to H-RS cells in vivo, based on the variable IL-1 staining of these cells in lymphoid tissues.

Animals↗
PubMed1989

Production of tumor necrosis factor-alpha and lymphotoxin by cells of Hodgkin's neoplastic cell lines HDLM-1 and KM-H2.

The production of tumor necrosis factors (TNF) from cells of two Hodgkin's Reed-Sternberg (H-RS) lines, HDLM-1 and KM-H2 was examined. The culture supernatant from these two types of H-RS cells exerts a cytotoxic effect on L929 cells. Both tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) are responsible for this activity. This was confirmed by the presence in the cells of proteins and m-RNAs of TNF-alpha and TNF-beta, as determined with immunoperoxidase staining and Northern blot hybridization. Approximately 20% of HDLM cells and 5% of KM-H2 cells were positively stained by a monoclonal anti-TNF-alpha antibody, and this staining was inhibited by preabsorption of the antibody with recombinant TNF-alpha. Staining with anti-TNF-beta, however, showed an intense reaction in more than 60% of HDLM-1 cells, but only in 5% to 10% of KM-H2 cells. The abundant expression of TNF-beta in HDLM-1 cells is consistent with approximately 10 times the TNF activity in HDLM-1-conditioned medium as compared with that of KM-H2. The rich secretion of TNF-beta in HDLM-1 cells was also validated by the inhibition of most of the TNF activity in HDLM-1-conditioned medium with anti-TNF-beta antibody, and by the presence of abundant TNF-beta mRNA in HDLM-1 cells. The reason for the abundant production of TNF-beta in HDLM-1 cells is not yet known, but may be attributable to a chromosomal abnormality in the 6p21 region. The expression of TNF-alpha, but not TNF-beta, by H-RS cells was demonstrated in lymph nodes from patients with Hodgkin's disease. The capacity of H-RS cells to secrete TNF as well as other cytokines, such as interleukin-1, colony-stimulating factors, and transforming growth factors, may contribute to the unique clinical and histopathologic alterations in patients with Hodgkin's disease.

Adult↗
PubMed1988

Establishment of human mesothelioma cell lines (MS-1, -2) and production of a monoclonal antibody (anti-MS) with diagnostic and therapeutic potential.

We have established and characterized two mesothelioma cell lines, MS-1 and MS-2, in four attempts at long-term culture of these cells. Both MS-1 and MS-2 cells consistently express cytokeratin and vimentin, and both have long, slender microvilli. The cells that grew indefinitely (MS-1, MS-2) had a higher DNA index and a higher nucleus:cytoplasm ratio than did those cells that failed to grow (MS-3, MS-4). All mesothelioma cells, both in short- and in long-term culture, responded to phorbol ester induction by displaying morphological differentiation, such as an increase in the number of microvilli. The distribution of vimentin and cytokeratin in the cells, however, remained the same regardless of the growth pattern or the phorbol-ester treatment of the cells. We have used MS-1 cells to produce a monoclonal antibody (anti-MS) that reacts with mesothelioma cells, but rarely with reactive or normal mesothelial cells or with cells of normal tissues. The antibody does not induce the modulation of antigen, and it causes no direct or complement-mediated cytotoxicity of MS-1 or MS-2 cells. If a toxin or an isotope conjugate of the antibody is used, it may be valuable in the near future to test it for use in immunoimaging or immunotherapy.

Antibodies, Monoclonal↗
PubMed1988

Expression of sialylated Leu-M1 antigen in histiocytosis X.

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Adult↗
PubMed1988

Expression of prostaglandin H synthase (cyclooxygenase) in Hodgkin's mononuclear and Reed-Sternberg cells. Functional resemblance between H-RS cells and histiocytes or interdigitating reticulum cells.

The synthesis of prostaglandin, prostacyclin, and thromboxane, which requires the enzyme prostaglandin H (PGH) synthase (cyclooxygenase), is a general property of histiocytes, monocytes, and Langerhans cells. Previously the authors reported the production of prostaglandin E2 in a Hodgkin's cell line, KM-H2, and suggested that these cells therefore have a functional similarity to histiocyte-related cells. The present study confirms that the Hodgkin's neoplastic (Reed-Sternberg, H-RS) cells in tissue are also capable of producing prostaglandins by demonstrating the presence of PGH synthase in these cells in B5-fixed, paraffin-embedded tissue sections. It was found that the H-RS cells from seven of ten patients with Hodgkin's disease were stained variously with anti-PGH synthase antibodies. In normal and reactive lymphoid tissues, anti-PGH synthase staining was restricted to histiocytes, endothelial cells, and interdigitating reticulum cells. Thus, this study provides further evidence for a possible relationship between H-RS cells and histiocytes or interdigitating reticulum cells; this relationship has also been supported by information obtained in extensive immunologic, biochemical, and cell-differentiation studies. The secretion of PGH-synthase products, especially prostaglandin E2, in H-RS cells may play a major role in the regulation of cellular immunity in patients with Hodgkin's disease.

Cell Line↗
PubMed1988

Reed-Sternberg cells in Hodgkin's cell lines HDLM, L-428, and KM-H2 are not actively replicating: lack of bromodeoxyuridine uptake by multinuclear cells in culture.

We compared the proliferation of mononuclear and multinuclear cells in four Hodgkin's cell lines, HDLM-1, HDLM-1d, L-428, and KM-H2, by examining their capacity to incorporate bromodeoxyuridine (BrdUrd) into nuclei. Approximately 5% of all cells in HDLM-1 cultures had two or more nuclei, a characteristic of Reed-Sternberg (RS) cells. Unlike mononuclear Hodgkin's (H) cells, these RS cells exhibited no uptake, or only minimal uptake of BrdUrd, suggesting that they did not replicate actively. Cytogenetic study showed that 25% of the HDLM-1 cells contained a tetraploid (4X) set of chromosomes with a characteristic two-peak distribution. Following treatment of HDLM-1 cells with phorbol ester, the percentages of 4X cells and RS cells increased to 50% and 12%, respectively. This increase in RS cells was not likely to be due to cell fusion as shown by the absence of hybridization of BrdUrd-positive and -negative nuclei. Phorbol ester has a short-term effect of blocking the exit of cells from G1 into S phase, but no effect on the transition from S phase to G2/M phase. The block is more prominent in 2X cells than in 4X cells, which may explain the increase in percentage of 4X cells in phorbol ester-treated cultures. In addition, phorbol ester induced the differentiation of H-RS cells, which was accompanied by loss of the marker HeFi-1 from the cell surface. Approximately one third of the RS cells did not express HeFi-1, or expressed only minimal amounts. The findings led us to the following conclusions: (1) The 4X cells probably are formed from 2X H cells as a result of disturbed cytokinesis, but not a cell fusion. (2) A considerable number of 4X cells were H cells, because the number of 4X cells consistently exceeded that of RS cells. (3) Since mitotic figures are extremely rare in RS cells and these cells did not show active BrdUrd uptake, the increased number of RS cells must also be a consequence of disturbed cytokinesis of H cells or a result of nuclear transformation (twisting, convolution, or separation of the nucleus) in H cells. (4) Most RS cells lose their proliferating capacity and some RS cells may undergo further differentiation. Uptake of BrdUrd and phorbol ester induction were also studied on the other three H-RS cell lines, HDLM-1d, L-428, and KM-H2, with results similar to those for HDLM-1.

Biological Transport↗
PubMed1987

Induction of differentiation of African Burkitt's lymphoma cells by phorbol ester: possible relation with early B cells.

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) was used to examine the phenotypic changes in three African Burkitt's lymphoma cell lines, P3HR1, Daudi, and Raji. Cells were cultured with a nanogram concentration of TPA for up to seven days and then analyzed by flow cytometry and an immunoperoxidase staining method. The cells were stained with a panel of monoclonal antibodies reactive with B lymphocytes or B cell leukemia/lymphomas, and an antibody to the enzyme terminal deoxynucleotidyl transferase (Tdt). All three cell lines were found to express more HLA-linked DC/DS (Leu 10) antigen, while demonstrating a concomitant decrease in the expression of common acute lymphoblastic leukemia antigen (CALLA) and terminal deoxynucleotidyl transferase after TPA induction. The other antigens including Ig, BA1, BA2, Tac, Leu 8, Leu 1, C3bR, Leu 12, and Leu M5 showed no significant changes. The marker expression and differentiation pattern of these African Burkitt's lymphoma lines are very similar to those of pre-B cells except for the surface IgM expression observed in Daudi cells. The expression of CALLA and Tdt in African Burkitt's lymphoma is probably not the result of an Epstein-Barr virus infection, but may in fact reflect the true nature or origin of tumor cells. We conclude that African Burkitt's lymphoma cells are derived from an early stage of B-cell differentiation closely related to, but more mature than pre-B cells.

Antigens, Neoplasm↗
PubMed1987

The H-RS-like cells in infectious mononucleosis are transformed interdigitating reticulum cells.

The lymphoid tissues from patients with infectious mononucleosis or, less frequently, with other reactive conditions may contain Reed-Sternberg (RS)-like cells. These tissues also contain cells resembling the lacunar cells or lymphocytic/histiocytic (L/H) variants, which are present in the lymphocyte-predominant type of Hodgkin's disease. The phenotype of these RS- and L/H-like cells was determined with a large panel of antibodies and lectins. The cells expressed sialylated Leu-M1, Con A, LN-2, and, less frequently, interleukin-1, S-100, and peanut agglutinin receptor. They reacted negatively with two markers for RS cells, Ki-1 and HeFi-1. These RS-like cells were consistently negative for T- and B-cell markers, including immunoglobulins. The markers of the RS-like cells are distinctly different from those in B-immunoblasts, but closely resemble those in interdigitating reticulum cells. It is concluded that interdigitating reticulum cells, when stimulated, can be transformed into lacunar-, L/H-, or RS-like cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Effect of monoclonal antibodies anti-2H9, anti-IRac, and anti-HeFi-1 on the surface antigens of Reed-Sternberg cells.

The interaction of 3 monoclonal antibodies (MAbs)--anti-HeFi-1, anti-2H9, and anti-IRac--with Reed-Sternberg (RS) cells was examined in vitro. MAb anti-2H9 induced specific modulation of the corresponding antigen (Ag) from the cell surface. Cell-bound anti-2H9 antibody (Ab)-Ag complexes rapidly disappeared during incubation of cells at 37 degrees C for 2-4 hours. This early loss was followed by reappearance of the Ag on the cell surface within 4-12 hours. In contrast, anti-HeFi-1 and anti-IRac bound avidly to the surface of RS cells and persisted for more than 3 days. During this period, there were no significant changes in the expression of HeFi-1 or IRac Ag on the surface of tumor cells. Cell surface-bound Abs were distributed uniformly, and there was no evidence of microaggregation, as determined by electron microscopy. None of the 3 MAbs was directly cytotoxic or exhibited complement-mediated cytotoxicity. On the basis of these findings (persistence of anti-HeFi-1 and anti-IRac on the cell surface), these 2 MAbs may be suitable for immunoimaging and immunotherapy for Hodgkin's disease.

Antibodies, Monoclonal↗
PubMed1987

Phenotypic expression of cells of stationary elements in human lymphoid tissues. A histochemical and immunohistochemical study.

The stationary elements of lymphoid tissues are composed of four types of cells: histiocytes, interdigitating reticulum cells, follicular dendritic cells, and fibroblastic reticulum cells. The phenotypes of these cells were determined with a large panel of monocyte/histiocyte, C3 receptor monoclonal antibodies, and others. Based on the monocyte-marker expression, histiocytes can be separated into two groups: (1) free histiocytes (monocyte-marker positive) and (2) fixed histiocytes (monocyte-marker negative). The former are characterized by the expression of monocyte markers, such as OK M1, Co Mo2, BRL Mol/Mo2, and Leu M3, whereas the latter are not. Interdigitating reticulum cells are localized in the T-cell zone. These cells are characterized by the expression of 1E9, 2H9, and Leu M1. Interdigitating reticulum cells and fixed histiocytes are similar in terms of marker expression and enzyme histochemistry. However, in interdigitating reticulum cells, the Leu M1 antigen is localized on the membrane, in contrast to histiocytes, in which it has a Golgi distribution. Follicular dendritic cells are present in germinal centers and mantle zones. These cells express complement (C3) receptors and several monocyte markers (including OK M1 and Co Mo2). Follicular dendritic cells are capable of trapping antigens onto their membranes. This unique property makes us reluctant to conclude that follicular dendritic cells are related to monocytes. Fibroblastic reticulum cells express BA-1 and alkaline phosphatase, and they form a dendritic network, especially in the T-cell zone. The results of this study demonstrate that immunoperoxidase staining with monoclonal antibodies can reveal the distribution of histiocytes and dendritic/reticulum cells in lymphoid tissues.

Antibodies, Monoclonal↗
PubMed1987

Localization of interleukin-1 in normal or reactive lymphoid tissues and skin: abundance of IL-1 in interdigitating reticulum cells.

The distribution of interleukin 1 producing cells was determined in the human lymphoid tissues and skin using immunohistochemical staining and a rabbit anti-interleukin-1 antibody. Interleukin-1 was detected mainly in the interdigitating reticulum cells localized in the T cell zone. Approximately, 10-30% of the histiocytes were also positively stained by anti-interleukin-1. The results suggests that interdigitating reticulum cells may play an important role in the initiation and amplification of T-cell immunity.

Animals↗
PubMed1987

Extracellular matrix does not induce the proliferation, but promotes the differentiation, of Hodgkin's cell line HDLM-1.

Tumor cells from the Hodgkin's cell line HDLM-1 were cultured in extracellular matrix (ECM)-coated flasks. Within 24 hours, the cells underwent rapid differentiation, accompanied by morphologic and phenotypic changes. A slow and less prominent, but similar change was observed in HDLM-1 cells after they had been induced with phorbol ester for 5 days. The ECM-induced cells became HeFi-1-negative and expressed antigens 2H9 and 1E9 on their nuclear membranes. These cells had punctate acid-phosphatase and esterase activities. Approximately 70% of the ECM-induced cells were elongated and had long, blunt cytoplasmic projections. These findings, together with evidence the authors previously presented, indicate that H-RS cells are related to interdigitating reticulum cells. The authors believe that the ECM-induced HDLM-1 cells can be used as an important model for studies of the nature and cell lineage of Hodgkin's disease.

Antigens, Neoplasm↗
PubMed1986

Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease.

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV-transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.

Animals↗
PubMed1986

Biochemical and ultrastructural study of Leu M1 antigen in Reed-Sternberg cells: comparison with granulocytes and interdigitating reticulum cells.

A group of monoclonal antibodies was shown to react with glycoconjugates containing a sugar sequence--lacto-N-fucopentaose III (LNF-III)--in granulocytes and in some normal nonlymphoid cells. The antibodies including anti-Leu M1, anti-My-1, WGHS 29-1, 534F-8, and 538F-12 of the immunoglobulin M-type were used to study the biochemical properties of LNF-III antigens in granulocytes, interdigitating reticulum cells, and neoplastic cells of Hodgkin's disease. In contrast to the presence of an abundant LNF-III glycolipid in granulocytes, the Hodgkin's neoplastic cells had no LNF-III glycolipid or contained only minimal amounts; however, both LNF-III glycoconjugates isolated from Hodgkin's neoplastic cells and interdigitating reticulum cells appeared to be a similar, if not an identical, 150,000-molecular-weight glycoprotein. The neoplastic cells in Hodgkin's disease appeared to show a biochemical property more closely related to interdigitating reticulum cells than any other cells in the monocyte-granulocyte-histiocyte system.

Antibodies, Monoclonal↗