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L P Sashchenko

Publications and source records attributed to L P Sashchenko.

At least 19 recordsLinked to original sources
PubMed2002

Anti-DNA autoantibodies reveal toxicity to tumor cell lines.

Cytotoxicity of anti-DNA autoantibodies from sera of SLE and CLL patients was assayed on permanent cell lines L929, HL-60, Raji, and K562. L929 cells appeared to be the most sensitive to antibody treatment. DNA-hydrolyzing properties of the same autoantibody preparations were analyzed in parallel. The data obtained outlined the correlation between cytotoxicity and DNA-hydrolyzing properties of these autoantibodies. It was shown that treatment of the cells with cytotoxic anti-DNA autoantibodies induced internucleosomal DNA fragmentation and Annexin V binding to the cell surface characteristic of apoptotic pathway of cell death. A time-dependent profile of antibody-mediated toxicity to L929 cells suggested recruitment of at least two distinct mechanisms of cell death. The first peak of cell death observed in 3 h of incubation was completely inhibited by preincubation of cells with caspase inhibitor YVAD-CHO, while the second increase in cell mortality (18-30 h) persisted. Possible mechanisms for anti-DNA autoantibody cytotoxicity are discussed.

Antibodies, Antinuclear↗
PubMed2000

Nonlymphoid cultured cells possess a system controlling cellular compatibility.

We show that various nonlymphoid cultured cells can activate the production of cytotoxic factors in response to direct contact with cells of a different kind. Accumulation of cytotoxic factors in the medium was detected 1 h after contact of K562 and L929 cells or after contact of L929 cells with purified membranes of K562 cells. TNF-alpha or immunologically related proteins, or both, but not Fas-ligand or lymphotoxin, were also accumulated in membranes of K562 and L929 cells shortly after these cells had been allowed to contact each other. The cytotoxic factors expressed by nonlymphoid cells trigger apoptosis of target cells. These observations strongly suggest that nonlymphoid cells possess molecular mechanisms controlling cellular compatibility.

Animals↗
PubMed1998

Novel functional activities of anti-DNA autoantibodies from sera of patients with lymphoproliferative and autoimmune diseases.

DNA-hydrolyzing activity of IgG autoantibodies from sera of patients with various types of lymphoproliferative diseases was investigated. The association of DNA-hydrolyzing activity with the antibody (Ab) fraction has been proved by newly developed affinity-capture assay. Study of abzyme incidence in blood tumors and systemic lupus erythematosis (SLE) revealed linkage of anti-DNA Ab catalysts to mature B-cell tumors, and increased probability of DNA-abzymes formation on the background of autoimmune manifestations. These data suggest possible similarity between mechanisms of abzyme formation in SLE and B-cell lymphomas. A new mechanism of formation of DNA-specific catalytic Abs has been proposed based on the increased crossreactivity of polyclonal DNA-abzymes to DNA-depleted nuclear matrix proteins. The possibility of the abzyme production as Ab to the energetically destabilized ground state of the antigen has been discussed. Preliminary results were obtained that indicate the complement-independent cytotoxicity of anti-DNA autoantibodies isolated from blood of patients with SLE and chronic lymphocytic leukemia.

Antibodies, Antinuclear↗
PubMed1997

Joint cultivation of human erythroblastoid cells and mouse fibroblasts triggers release of a wide spectrum of cytotoxic factors.

It has been demonstrated that joint cultivation of human K-562 cells and mouse L-929 cells results in triggering apoptosis in L-929 cells and possibly also in K-562 cells. Analysis of proteins recovered from the culture medium has revealed the presence of three cytotoxic factors including TNF-alpha. This is the first observation of a release of cytotoxic factors by non-lymphoid cells in response to a direct contact with cells of different origin.

Animals↗
PubMed1997

Apoptotic and necrotic cytolytic processes induced by membrane associated proteins of LAK cells.

Cytolytic processes induced by membrane-associated proteins of human lymphokine-activated killer (LAK) cells with different phenotypes (CD3+, CD16-, CD8+ and CD16+, CD8+, CD3-) were studied using L929 and K562 types of target cells. Independently of the phenotype of effector cells and the type of target cells, total fractions of membrane proteins induced several different cytolytic processes occurring with different rates and involving different mechanisms of genome fragmentation. The membrane fraction induced, irrespective of the phenotype of LAK cells, mostly apoptotic processes in the L929 line. At the same time, cytolytic processes induced in K562 line differed by the mechanisms of DNA fragmentation. An inhibitor of lysosome activation, NH4Cl, and a Ca(2+)-binding reagent, ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), induced partial inhibition of short-term cytolytic processes (developing within 1-5 h) but did not affect the development of long-term cytolytic processes requiring more than 6-8 h for their development.

Apoptosis↗
PubMed1996

Different pathways of the release of cytotoxic proteins in LAK cells.

Human LAK cells were shown to release cytotoxic proteins by both Ca(2+)-dependent and Ca(2+)-independent mechanisms. CD3+ CD8+ CD16- and CD16+ CD8+ CD3- LAK cells were co-incubated with target cells in the presence of 4 mM EGTA. Although EGTA inhibited the exocytosis of cytolytic granules, supernatants obtained were cytotoxic for target cells. Cytotoxicity of CD3+ LAK cells and CD16+ LAK cells was due to cytotoxic proteins with MW 75 (p75), 35 (p35) and 22 (p22) kDa. LAK cells were also shown to release cytotoxic proteins by way of continuous secretion. After co-incubation in the absence of target cells LAK cells can secrete cytotoxic proteins with MW 75 (p75), 55 (p55), 38 (p38), 35 (p35), 25 (p25), 22 (p22) and 17 (p17) kDa.

CD3 Complex↗
PubMed1994

Albumin-like glycoprotein from human fetal tissue.

Albumin-like glycoprotein (Gp66) with a molecular mass of 66 kDa has been isolated from human fetal tissue by size-exclusion, ion-exchange chromatography and reverse-phase HPLC. Reactivity of Gp66 with antiserum raised against the major protein components fraction of human fetal serum was observed. The N-terminal 35 amino acid residues of Gp66 were identical to human serum albumin. Meanwhile Gp66 differed from albumin by a/ the presence of 3-5 Trp residues instead of 1 according to fluorescence and UV-spectra, b/ the glycosylation pattern: bi-, tri-, and tetraantennary sialooligosaccharides of a complex type were present. Isoelectric focusing revealed 4 isoforms (pI ranging within 4.8 to 5.1) of Gp66. Gp66 (but not asialo-Gp66) was able to inhibit the cytotoxic effect of TNF against the tumor cell line L929. Inhibition of WEHI-3 and L929 tumor cells proliferation by Gp66 was similar to that of albumin.

Animals↗
PubMed1993

The role of apoptotic and necrotic processes in cytolysis mediated by LAK cells with different phenotypes.

The role of necrotic and apoptotic pathways in cytolysis mediated by LAK cells was studied. The contribution of necrotic and apoptotic processes to cytolysis depends both on the LAK cells' phenotype and the type of target cells. CD16+/CD8+/CD3- LAK cells induced necrosis of K562 and L929 target cells. The cell death induced by CD3+/CD8+/CD16- LAK cells was found to include features of apoptotic and necrotic processes.

Antigens, CD↗