The role of interleukin 2 and T11 E rosette antigen in activation and proliferation of human NK clones

Although considerable data have recently been accumulated regarding the functional role of natural killer (NK) cells, relatively little is known about the factors that regulate NK cell activity. In these studies, we evaluated the role of interleukin 2 (IL 2) and the expression of the IL 2 receptor in the activation and proliferation of human NK cloned cell lines. By using a series of cloned cell lines, we were able to analyze homogeneous populations of NK cells that ordinarily comprise only a small fraction of peripheral blood lymphocytes and are extremely heterogeneous with respect to phenotypes and cytotoxic specificities. In comparison with several T cell clones, we found a much lower density of IL 2 receptors on NK clones, regardless of whether or not these cloned cells had a mature T cell phenotype. Correspondingly, NK clones needed a 10-fold higher concentration of recombinant IL 2 for maximal proliferation. Moreover, blocking studies with specific monoclonal IL 2 receptor antibodies indicated that IL 2 is both necessary and sufficient to induce the proliferation of NK clones. Because the majority of peripheral blood NK cells and NK clones express the T11 E rosette receptor antigen, which has been shown to be an antigen-independent activation pathway for T cells, we were able to study the role of monoclonal anti-T11 antibodies in the activation of various NK clones for which a specific target antigen is not known. In contrast to T cell clones, the induction of IL 2 receptor expression after T11 activation was possible only for some NK clones such as JT10 and JT3, but not for CNK5. Before activation, the IL 2 receptor expression of NK clones was confined to cells in the G2 - M phase, but after T11 activation the more pronounced IL 2 receptor expression became independent of the cell cycle. With respect to the direct proliferative effect of anti-T11 activation that has been noted with T cell clones, only the T3+ (JT10) and not the T3- NK clones could be directly stimulated. Nevertheless, IL 2 receptor expression could be triggered on some T3- clones such as JT3. Because T11-induced proliferation of T cells has been shown to be dependent on both the expression of the IL 2 receptor and on the interaction of this receptor with IL 2, it is proposed that the different responses of NK cells to T11 activation may reflect the ability of the individual clone to produce endogenous IL 2, as well as its ability to express the IL 2 receptor.     

Neurotoxic,cytotoxic, apoptotic and antiproliferative effects of some marine algae extracts on the NA2B cell line

Oxidative stress contributes to cancer pathologies and to apoptosis. Marine algae exhibit cytotoxic, antiproliferative and apoptotic effects; their metabolites have been used to treat many types of cancer. We investigated in culture extracts of Petalonia fascia, Jania longifurca and Halimeda tuna to determine their effects on mouse neuroblastoma cell line, NA2B. NA2B cells were treated with algae extracts, and the survival and proliferation of NA2B cells were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of algae extracts on oxidative stress in NA2B cells also were investigated using nitric oxide synthase (NOS) immunocytochemistry and apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling. We observed significant neurite inhibition with moderate damage by the neurotoxicity-screening test (NST) at IC₅₀ dilutions of the extracts. MTT demonstrated that J. longifurca extracts were more toxic than P. fascia and H. tuna extracts. We found an increase of endothelial and inducible NOS immunostaining for oxidative stress and TUNEL analysis revealed increased apoptosis after application of extract. Our findings suggest that the algae we tested may have potential use for treatment of cancer.     

Health and the life course: why safety nets matter.

This article argues that a life course approach is necessary to understand social variations in health. This is needed in order to take into account the complex ways in which biological risk interacts with economic, social, and psychological factors in the development of chronic disease. Such an approach reveals biological and social "critical periods" during which social policies that will defend individuals against an accumulation of risk are particularly important. In many ways, the authors of modern welfare states were implicitly addressing these issues, and the contribution of these policies to present day high standards of health in developed countries should not be ignored.     

Regulators of complement activity mediate inhibitory mechanisms through a common C3b‐binding mode

Regulators of complement activation (RCA) inhibit complement‐induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i–iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b‐binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100° rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease‐related mutations and immune evasion.     

Production and characterization of polyclonal and monoclonal antibodies against Aflatoxin B1 oxime-BSA in an enzyme-linked immunosorbent assay

From a single aflatoxin B₁ oxime — bovine serum albumin conjugate, polyclonal and monoclonal antibody preparations were produced. The four rabbit polyclonal antisera were specific for aflatoxin Bi in a microtitration plate enzyme — linked immunosorbent assay. The monoclonal antibodies showed a wide range of differing specificities, recognizing, for example, aflatoxins B₁, B₂, G₁ and G₂; B₁ and B₂; B₁ and G₁; and G₁ alone. No antibody preparations reacted with aflatoxin M₁. The significance of these results to the strategy of anti-aflatoxin antibody production for use in quantitative enzyme immunoassays is discussed.     

Roentgenographic and direct measurement of femoral cortical involution in a prehistoric Mississippian population

Recent roentgenographic studies suggest that periosteal apposition adds femoral cortical bone faster than it is lost by endosteal involution, so that cortical bone area increases with age. A comparison was made of direct and roentgenographic measurements of femoral cortical bone using femora from 23 females and 20 males of a prehistoric Mississippian population dated at A.D. 1540–1700. The comparison revealed that significant errors existed in the technique of radiographic measurement (p<0.000001), in estimating male and female cortical thickness (p<0.000001), and the changes in thickness with age (p<0.000001). There was no significant interaction of the variables: age, sex, and method. The errors arose partly from the inability of the roentgenograph to reveal clearly endosteal porosity, and partly in the assumption that the medial and lateral cortical wall thickness would be representative of the mean cortical thickness. The reduction in cortical thickness (11.3% males and 29.3% females) with age as measured directly is comparable with loss in modern populations.     

The nature of the sex-linked differences in glutathione peroxidase activity and aerobic oxidation of glutathione in male and female rat liver

1. Glutathione peroxidase activity in the livers of sham-operated female rats was about 60% higher than in similarly treated male rats. The value in the ovariectomized female was about the same as that in the castrated or sham-operated male. 2. Glutathione peroxidase activity changed during the oestrous cycle. The highest value was in oestrus, and was about 50% higher than the lowest activity, which was found in dioestrus. The activity in proestrus and in metoestrus was respectively about 20 and 30% higher than in dioestrus. 3. In the pregnant female 1 or 2 days before term, glutathione peroxidase activity was about 20% higher than that in the female in oestrus. 4. Subcutaneous implants of both oestra-diol and progesterone in the gonadectomized rats increased the glutathione peroxidase activity approximately to the values found in the female at oestrus. 5. The rate of aerobic oxidation of GSH in the female rat liver was about 80% higher than in the male and about 110% higher than in the gonadectomized rats. Treatment of gonadectomized rats with subcutaneous implants of oestradiol and of progesterone increased the rate of oxidation of GSH by about 100%. 6. In the presence of azide the rate of GSH oxidation in the male and in the female was respectively about 3.5- and 2.1-fold that in the absence of azide. In castrated or ovariectomized rats the increase due to the presence of azide was about 2.4-fold. In the gonadectomized rats treated with oestradiol or progesterone the rate of GSH oxidation in the presence of azide was about 2.2-fold that in its absence. 7. The rate of lipid peroxidation in female was 15-30-fold that in male or in gonadectomized rats. Treatment of the gonadectomized rats with oestradiol or with progesterone increased the rate of lipid peroxidation up to values that were even higher than in the female. In the presence of GSH the formation of malonaldehyde from peroxides was virtually eliminated. 8. The results suggest that the sex-linked differences in glutathione peroxidase activity, in the rate of GSH oxidation and in the rate of lipid peroxidation are due to the female sex hormones. 9. It is suggested that both the catalase activity and the rate of hydrogen peroxide formation are higher in the male than in the female. 10. Sex-linked changes in glutathione peroxidase, in the rate of GSH oxidation and in the rate of lipid peroxide formation are discussed in relation to the metabolism of oestrogens in the liver and also to the possible nature of those sex-linked changes.