Search PubMed⌕ Search

Biomedical subjects

E Saksela

Publications and source records attributed to E Saksela.

At least 91 records · Page 5Linked to original sources
PubMed1983

Polarization of NK cell cytoskeleton upon conjugation with sensitive target cells.

We studied the cytoskeletal changes in natural killer (NK) cells during conjugate formation, i.e., when NK cells make contact with sensitive vs resistant target cells. F-actin and vinculin were seen to polarize at the contact sites upon conjugation with sensitive K562 cells, whereas in conjugates with resistant Raji target cells such an orientation was an infrequent finding. Myosin and two other cytoskeletal proteins, spectrin and vimentin, on the other hand, showed a random distribution in conjugating NK cells regardless of the target cell type. Hence the cytoskeletal redistribution associated with conjugation seems to be different from the receptor capping phenomenon, which is accompanied by clustering of actin, myosin, vimentin, and spectrin. On the basis of these results it seems probable that the lytic conjugate formation in NK-mediated cytotoxicity is associated with the formation of a specific type of junction that involves actin and vinculin. This cytoskeletal reorganization precedes and could be a prerequisite for the polarization of the cellular secretory apparatus and may be functionally responsible for the required cytokinetic movements.

Actins↗
PubMed1982

Umbilical-cord-blood-derived suppressor cells of the human natural killer cell activity are inhibited by interferon.

The natural killer (NK) activity of umbilical-cord-derived lymphocytes was studied. The general level of activity was lower than with adult lymphocytes against K-562 cells and fetal fibroblasts. The activity could be boosted by interferon pretreatment of effect or cells, fractionated with Percoll density gradient centrifugation, and the suppressive activity of different fractions was tested on highly enriched adult buffy-coat-derived NK cells. Allogeneic adult NK cell activity could be inhibited in 9 of 20 cases tested with small and medium-sized T lymphocytes (Percoll fractions 4-5) from the umbilical cord. The suppressive capacity was further enriched in fractions forming rosettes (RFC) with antibody-coated human erythrocytes (EA). Such EA-RFC of percoll fraction 4-5 from umbilical cord exerted a strong suppressive activity in each case tested. Pretreatment of EA-RFC with interferon regularly abolished the suppressive effect. We conclude that there are Fc-receptor-positive small/medium-sized T lymphocytes in the umbilical cord blood which can efficiency suppress the cytotoxic activity of NK cells and that the suppressive activity can be abolished by interferon pretreatment of the suppressor cells.

Adult↗
PubMed1982

Effect of a monoclonal anti-large granular lymphocyte antibody on the human NK activity.

A monoclonal hybridoma antibody of IgGIa subclass was produced by fusing NS-1 myeloma cells with spleen cells of a mouse immunized with human LGL cells. This hybridoma antibody, termed NK-8, was reactive by indirect immunofluorescence with 33% of peripheral blood LGL cells and 70% of LGL forming conjugates with K-562 cells. Monocytes, granulocytes, and other lymphocytes were nonreactive. In iodinated protein A binding assays NK-8 was nonreactive with all kinds of leukemia and lymphoma lines tested and showed activity only against LGL cells. NK-8 inhibited the LGL-mediated cytotoxicity against K-562 cells by 50 to 60% without complement and inhibited the K-562 induced interferon production from the LGL population. However, the spontaneous cytotoxicity against human skin fibroblasts was augmented if the effector cells were pretreated with NK-8.

Animals↗
PubMed1982

Ultrastructure of human natural killer cells: nature of the cytolytic contacts in relation to cellular secretion.

The ultrastructure of human NK cells, NK/target cell conjugates, and the effect of monensin, a secretion inhibitor, were studied. Human peripheral blood lymphocytes, highly enriched (75 to 85%) in large granular lymphocytes (LGL), which are known to be the mediators of human NK activity, were used as effectors, and K562 cells as targets. LGL-type of cells were characterized in electron microscopy by a low nucleocytoplasmic ratio, indented nucleus, several large mitochondria, prominent Golgi apparatus, and cytoplasmic osmiophilic granules bound by a unit membrane. Their surface was of intermediate villous type. Two types of effector/target contacts were seen: either effector cell protrusions were pushed deep into pouches and lacunae of the target cell surface, or a wide area of intimate cell-to-cell contact was formed. The contact formation was followed by polarization of the effector cell Golgi apparatus towards the contact area. Monensin, a carboxylic ionophore, which interrupts the vesicular traffic of Golgi-derived vacuoles to the cell surface, caused an accumulation of cytoplasmic vesicles in the LGL but had no effect on the effector/target contact formation. Monensin inhibited the NK lysis apparently via cessation of secretion by the LGL. It did not affect the viability of the effector cells. The lytic steps of human NK cells thus involve binding to the target cell, polarization of cytoplasmic organelles towards the target, and apparently a precisely directed exocytosis of secretory material.

Cell Communication↗
PubMed1982

Colposcopic and histologic findings in cervical chlamydial infection.

Colposcopic and histologic findings in 41 patients with Chlamydia trachomatis-associated cervicitis and in age-matched controls with nonspecific cervicitis are presented. Colposcopy showed exophytic follicular cervicitis in 30 patients in the chlamydia group and in none in the control group. Atypical transformation zone occurred significantly more often in the chlamydia group. Directed biopsy specimens revealed cervical intraepithelial neoplasia in 10 cases in the chlamydial group but in only 1 case in the control group. In 4 patients with chlamydial cervicitis lymphoid follicles were observed in histologic specimens.

Adult↗
PubMed1981

Teratogenic hazards of oral contraceptives analyzed in a national malformation register.

During the period 1967-1976, prospectively collected data were available in the Finnish Register of Congenital Malformations on the contraceptive usage of 3,002 mothers of children with malformations detected at birth, as well as of time-matched and place-matched control mothers. The distributions of the various types of malformations were similar among contraceptive users (immediately prior to or during the pregnancy) and nonusers. The total incidences of various methods of contraception were also similar among mothers of malformed children and the control mothers. The risk ratio method for matched pairs allowed us to evaluate the strength of the observed negative correlation concerning oral contraceptives. Thus, we could exclude with 95% confidence any effect larger than 5% of oral contraceptives on the incidence of visible malformations.

Abnormalities, Drug-Induced↗
PubMed1980

Isolation of human NK cells by density gradient centrifugation.

Sedimentation characteristics of human NK cells in discontinuous Percoll density gradients were studied. NK activity against the leukaemic cell line K-562 peaked in a single low density fraction mainly consisting of large granular lymphocytes previously shown to be the principal NK cells in human peripheral blood. Percoll density gradient centrifugation provides a useful tool for analysis of human NK cells and their relationship to other blood mononuclear cells.

Cell Fractionation↗
PubMed1980

Induction of autologous reactivity of human NK cells.

'Mature' human natural killer cell activity could be enriched by adsorption-elution with fetal fibroblast as adsorbents against normal allogeneic skin fibroblasts, but not against autologous targets. However, when the natural killer activity was augmented by contact with tumour cells (HeLa), autologous and allogeneic skin fibroblast targets were killed without preference. Adsorption-elution with augmenting target cells as adsorbents resulted in an efficient enrichment of NK activity showing non-discriminate cytotoxicity. Morphologically, this was associated with an enrichment of large granular lymphocytes previously shown to be responsible for human NK activity. We conclude that the NK activity of human 'mature' NK cells shows a relative autologous exemption, whereas 'pre-NK' cells augmented to full activity in vitro are non-discriminative.

Adsorption↗