The human LT system

Granger, Gale A.; Yamamoto, Robert S.; Fair, Daryl S.; Hiserodt, John C.

doi:10.1016/0008-8749(78)90069-2

Cited by 75 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The LT molecules within each animal species examined are heterogeneous with respect to size and charge (1). Immunological and biochemical studies in both the human, murine, and guinea pig LT systems have determined that certain but not all of the various molecular weight LT classes are an interrelated family of molecules (2,3). Further biochemical analysis of the interrelated human LT components has revealed that one of two possible situations exists.…”

Section: Introductionmentioning

confidence: 99%

Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Weitzen

Yamamoto

Granger

1983

Cellular Immunology

View full text Add to dashboard Cite

Supematants obtained from lectin-restimulated, preactivated, human peripheral blood lymphocytes rapidly released (5-24 hr) high levels of lymphotoxin (LT) activity in vitro. Peripheral blood lymphocytes were preactivated by coculturing with either fetal calf serum or with allogeneic continuous B-cell lines (LCCL) which were treated with mitomycin C. These supematants contained a population of L-929 cell-lytic LT forms which also selectively bind to the NK-sensitive K-562 cell. However, lytic LT forms for L-929 cells from cPBL and LCCL cultures did not bind to the NK-sensitive MOLT-4 or NK-resistant Raji cells. Additional studies reveal these supernatants contain a second set of LT forms which have cell-binding and cell-lytic activity detectable on MOLT-4 and K-562 cells in a 12 to 18 hr "Cr-release. assay. Cell-lytic form(s) for the MOLT-4 and K-562 cells were not stable for more than a week at -20°C. These findings indicate that materials with LT activity are heterogeneous with respect to their capacity to recognize common and discrete cell-surface components on different types of target cells in vitro.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Weitzen

Yamamoto

Granger

1983

Cellular Immunology

View full text Add to dashboard Cite

show abstract

“…Granger et al (15) have also reported that species of lymphotoxin exist in higher molecular weight forms. It seems likely that there is a family of cytotoxic factors with TNF activity and that lymphotoxin and TNF(LuKII) are members of this family.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of a human tumor necrosis factor from the LuKII cell line.

Rubin¹,

Anderson²,

Sullivan³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A factor with tumor necrosis factor (TNF) activity produced by the LuKII human lymphoblastoid cell line [designated TNF(LuKII)] was purified sequentially by using controlled-pore glass, lentil lectin-Sepharose, and procion red agarose chromatography, yielding TNF with a specific activity of 1.5 X 10(7) units per mg of protein and an isoelectric point of approximately equal to 6.7. Purified TNF(LuKII) fractionated by NaDodSO4/PAGE under reducing as well as nonreducing conditions was found to contain seven protein bands of Mr 80,000, 70,000, 43,000, 25,000, 23,000, 21,000, and 19,000. The proteins of Mr 80,000 and 70,000 could not be dissociated into lower molecular weight components. Peptide mapping analysis and immunoblotting analysis revealed that the seven protein bands in the purified TNF(LuKII) preparations are related. After fractionation of TNF(LuKII) by NaDodSO4/PAGE under reducing conditions, TNF activity was recovered from the regions of Mr 70,000 and 19,000-25,000. Purified human TNF(LuKII) (i) produces hemorrhagic necrosis of Meth A mouse sarcoma in the standard in vivo mouse TNF assay; (ii) has the same pattern of reactivity as mouse TNF (cytotoxic/cytostatic/no effect) on a panel of human cancer cell lines; and (iii) has its anticellular effect potentiated by interferon, also a feature of mouse TNF.

show abstract

“…Extensive studies reveal the LT forms in these supernatants are heterogeneous in their size (14,15), cell-lytic capacity (3,11,16,17), and their ability to bind to different cell types in vitro (3,6,17). One possible explanation for this effect is that the lectin signal stimulates the release of discrete LT forms from different classes of effector cells; i.e., NK, anomalous T killers, and/ or specific cytotoxic lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of human NK-induced cell lysis and soluble cell-lytic molecules with anti-human LT antisera and various saccharides

Weitzen

Innins

Yamamoto

et al. 1983

Cellular Immunology

View full text Add to dashboard Cite

The present study examines and compares the cytolysis of K-562 and MOLT-4 cells mediated by human natural killer (NK) cells from fresh peripheral blood and lymphotoxins (LT) derived from human lymphoid cell populations after lectin stimulation in vitro. Lymphotoxins were obtained from 5-hr concanavalin A (Con A)-restimulated human peripheral blood lymphocytes (PBL) which were precultured for 5 days in medium and fetal calf serum or with allogeneic human B-lymphoid cell lines. Two classes of probes were employed in both direct (cell) and indirect (supernatant) induced target-cell lysis: (a) various saccharides and (b) antibodies reactive with human LT forms. Two sugars, N-acetylglucosamine and a-methylmannoside, were able to inhibit direct cell lysis of both MOLT-4 and K-562 target cells. However, saccharide inhibition was distinct for each type of target even when effector cells were obtained from the same donor. These same saccharides were also able to inhibit 20-30% of the total LT activity in a supematant for L-929 cells and 50-90% of the lytic activity on MOLT-4 cells. Anti-human F(ab')t (IgG) and rabbit anti-q LT sera blocked direct cell lysis of MOLT-4 and K-562 targets in 50% of the experiments. The anti-a* LT serum only recognizes a portion of the LT forms in these supernatants. These results reveal that, while both direct and indirect cell lysis are complex phenomena, they may both occur in some cases by a common mechanism(s).

show abstract

The human LT system

Cited by 75 publications

References 23 publications

Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Identification of human lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK-sensitive cell lines in vitro

Purification and characterization of a human tumor necrosis factor from the LuKII cell line.

Inhibition of human NK-induced cell lysis and soluble cell-lytic molecules with anti-human LT antisera and various saccharides

Contact Info

Product

Resources

About