Natural killer cell activity in patients with carcinoma of the larynx and hypopharynx.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
M Ghoneum
Publications and source records attributed to M Ghoneum.
A monoclonal antibody 1A6 to T-cell recognizes a common antigen expressed on lymphocytes from normal and leukemic patients, and inhibits NK cell activity.
A new monoclonal antibody (MAB), IA61gG2a, has been derived from Balb/c mice after immunization with T-cell chronic lymphocytic leukemia (T-CLL). This monoclonal antibody, 1A6 was tested on normal human peripheral blood cells, leukemia patients' cells and leukemia-lymphoma cell lines. The results demonstrated that this antibody reacts with normal human T and B cells, but not with erythrocytes, granulocytes or platelets. Further examinations showed 10/11 leukemic patient cell types were positive with 1A6. In contrast, many leukemia-lymphoma cell lines were negative (14/17), i.e. T and B leukemia lymphoma cell lines, non-T and non-B leukemia cell lines as examined by complement mediated cytotoxicity test and immunofluorescence test. Other prominent characteristics of 1A6 MAB have been demonstrated, which include inhibition of myeloid colony formation (CFU-C) and suppression of human natural killer cell cytotoxicity (NKCC). These results suggest that 1A6 is a common marker for normal T, B, NK cells and leukemic patients cells having T and B cell origin, but 1A6 antigen is not expressed on many leukemia lymphoma cell lines. Therefore, it could be useful for studying malignant transformation of lymphoid cells.
Animals↗
Change in tumour cell-lymphocyte interactions with age.
In the present study, we analysed the phenomenon of leukophagocytosis by tumour cells with respect to the age of the animal. Splenic leukocytes from C3H mice at different ages were depleted of macrophages and used as targets against tumour effector cells. Tumour cell lines P388D1, a macrophage lymphoma of mouse origin and LAZ-559, a B cell lymphoma of human origin, were cultured with leukocytes at 37 degrees C and 5 per cent CO2 for 4 h and the percentage of phagocytic tumour cells were examined in cytospin preparations. The results demonstrated that the phagocytic activity of P388D1 cells was 10, 6, 3 and 28 per cent against 1, 2, 6, and 35 week-old mice respectively; while LAZ-559 showed lower activity; 5, 3, 1.5 and 17 per cent against leukocytes of corresponding ages. Susceptibility of old leukocytes to phagocytosis could be detected as early as 30 min after culture with tumour cells, and increased with increasing incubation period. At 4 h, phagocytosis by tumour cells resulted in 38 and 29 per cent reduction in the leukocyte number postculture with P388D1 and LAZ-559 cells respectively. We postulate that an age-related decline in immune function is associated with increased level of phagocytic tumour cells, and that the loss of leukocytes may have adverse effects on the immune system.
Aging↗
Augmentation of macrophage phagocytosis by modified arabinoxylan rice bran (MGN-3/biobran).
MGN-3/Biobran, modified arabinoxylan rice bran, has been shown to be a potent biological response modifier (BRM) as manifested by stimulation of different arms of the immune system such as NK, T and B cells; however, its effect on macrophages has not yet been studied. The effects of MGN-3 on macrophage function was examined in vitro using 3 models: human macrophage cell line U937, murine macrophage cell line RAW264.7, and murine peritoneal macrophages (P-M phi). Treatment with MGN-3 resulted in an increase in the percentages of attachment and phagocytosis of yeast by macrophages. The effect depends on the type of macrophage and the dose of MGN-3 applied. Macrophages also demonstrated enhancement in their spreading ability, post treatment with MGN-3. Results also showed that MGN-3, in a dose dependent manner (1, 10,100 microg/ml), significantly induced high levels of production of cytokines: TNF-alpha; and IL-6. In addition, MGN-3 significantly increased nitric oxide (NO) production. This data demonstrates that MGN-3 is a potent inducer of phagocytic function by macrophage, and suggests that MGN-3 is a useful agent for fighting microbial infection.
Animals↗
Minimizing cancer risk using molecular techniques: a review.
This review article summarizes molecular markers that can signal enhanced risk of cancer and provide clinicians with these clues in order to attempt the use of natural and synthetic compounds to intervene in the early precancerous stages of carcinogenesis before invasive disease begins. With an aim such as this in mind, we have begun to apply molecular techniques based on many research articles to look for biomarkers capable of signaling a greater risk of cancer. It is possible to attain relatively quick answers by monitoring selected signs and damage in the body which provide the environment for abnormal cell growth and differentiation. These molecular techniques aim to uncover critical precancerous events taking place inside the body and identify measurable biologic flags signaling their occurrence. For years now, scientists have understood that the onset of cancer is a gradual, step-wise process that may unfold over the course of decades, rather than a single, fixed event that can be dated in a pathologist's report. Carcinogenesis usually encompasses the prolonged accumulation of injuries at several different biological levels and includes both genetic and biochemical changes in cells. At each of these levels there is an opportunity for intervention-a chance to prevent, slow or even halt the gradual march of healthy cells toward malignancy. It is estimated that 75% of cancers are induced by chemicals; thus, if exposure to chemicals is avoided, cancer can be prevented. Also, depending on the individual's genetic background, the ability to metabolize chemicals is different among the population. This means that, "you and I can be exposed to exactly the same amount of a chemical," yet our response will differ because we metabolize carcinogens differently due to different rates of deoxyribonucleic acid (DNA) repair, apoptosis, and mitosis or different levels of Phase I and Phase II detoxification enzymes. This, along with a more or less efficient immune system, may promote tumor formation or destroy a cancer cell at its earliest stage of development. Therefore, measurement of the biologic markers such as DNA and protein adducts, DNA damage, programmed cell death, DNA repair system, mitosis, gene activation, levels of antioxidants and efficient immune function described in this chapter and summarized in Figures 2 and 10, are biological clues indicating that the body has been assaulted by toxic (or cancer-causing) agents. This early identification of biomarkers for special vulnerability to the effects of chemicals and detection of selected signs of precancerous damage in the body may culminate preventive measures and the saving of lives.
Apoptosis↗
The effects of carcinogenic methylcholanthrene on carbohydrate residues of NK cells.
The present study examines the effect of methylcholanthrene (MCA), a a carcinogenic polycyclic hydrocarbon, on the carbohydrate receptor determinants (RD) on natural killer (NK) cell surface using the bead-coupled lectin assay. Murine NK cells exhibited different degrees of preferential binding to the specific lectins tested. Of the ten lectins tested, five exhibited a positive binding affinity while the remaining five exhibited no or insignificant binding. NK cells bind to beads derivatized with mannose specific lectins: Concanavalin A (Con A), Lens culinaris, and Pisum sativum. NK cells also bind to other lectin beads such as Triticum vulgaris (GalNac) and Vicia villosa (D-GlcNAc). All these lectin beads exhibited greater than 90% adhesion. The underivatized control beads exhibited no NK binding. The NK cells that were exposed to MCA for 2 h demonstrated a significant decrease in lectin bead-cell coupling in a dose dependent manner. MCA (10 micrograms/mL) caused a 17.8%, 40% and 4.7% decrease in binding affinity when introduced to the mannose specific lectins; Con A, L. culinaris and P. sativum beads, respectively. The binding of T. vulgaris and V. villosa to NK cells was inhibited (23.4% and 28%) by MCA treatment. An increase in the dose to 20 micrograms/mL resulted in a greater inhibition in binding affinity towards lectin beads. Con A, 35.3%, L. culinaris, 62.6%, P. sativum, 30.9%, T. vulgaris, 44.2% and V. villosa, 46.2%. The effect of MCA activation and cytotoxic response. Hydrolysis of PI metabolites (PIP and PIP2) cause generation of secondary messenger: inositol-1,4,5-triphosphate and diacylglycerol, both of which elicit an immune response through their products (Ca2+ and PKC) respectively. Identification of the relationship between receptor level, induction of second messenger and cytotoxic activity may resolve the molecular basis of suppression of NK cytotoxicity by MCA and other PAH compounds.
Animals↗
Immune alteration associated with exposure to toxic chemicals.
Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity.
Adult↗
Isolation of T lymphocyte subsets from peripheral blood using monoclonal antilymphocyte antibodies.
Monoclonal antisera against helper (serum OKT4) and suppressor (serum OKT8) T cells were employed in a complement-dependent lymphocytotoxicity reaction to isolate helper and suppressor T cells from peripheral blood mononuclear cells. When prepared by this method, helper and suppressor T cells had a purity of 67.8 percent and 78.8 percent, respectively. Approximately 56 percent of viable suppressor and 33 percent of viable helper T cells were lost during the procedure.
Antibodies, Monoclonal↗