Cytolytic activity

Modeling Pardaxin Channel. The remarkable switching of conformation in the presence of detergents or phospholipid vesicles (5) suggests that pardaxin is a very flexible molecule. This property helps to explain the apparent ability of pardaxin to insert into phospholipid bilayers. In addition, it is consistent with the suggestion that the deoxycholate-like aminoglycosteroids (5,7) present in the natural secretion from which pardaxin is purified (5) serve to stabilize its dissociated conformation. The question of the mechanism by which pardaxin assembles within membranes is important for understanding pore formation and its cytolytic activity (5). 

The natural killer cells (NK) are the host s primary innate immune responders against viral infections. Studies have shown morphine to suppress the cytolytic activity of NK cells (Shavit et al. 2004). In vivo studies carried out in the Indian rhesus macaques looked at chronic morphine administration and SIV the equivalent of HIV in apes. This group concluded that morphine contributed to the pathogenesis of Simian Immunodeficiency Virus (SIV) infection and that this contribution occurred in conjunction with the replication of viral proteins including Tat (Noel and Kumar 2006 Noel et al. 2006). 

Fungicidal activity was determined by the disc method and zones of inhibition were recorded by measuring the diameter (mm) of the inhibition zone. Yeast cultures (S. cerevisiae) showed growth inhibition (clear area surrounding disc) by sediment extracts from all stations when compared to control discs. HPLC analysis of sediment extracts showed more than 20 components in the migration profile of each station. Of these components, a fraction demonstrated to possess cytolytic activity in the crude extract (Ve = 24 ml) was present in all stations when compared to the migration profile of the active fraction (Figure 2). 

The interleukin-2 receptor (IL-2R) is important in that the cytokine IL-2, secreted by a subset of T-helper cells, enhances the proliferation of activated T and B cells and increases the cytolytic activity of natural killer (NK) cells and the secretion of IgG. 

Warren, T., Mitchell, K., and Lawrence, B.P., Exposure to 2,3,7,8-tetrachlorodibenzo-p dioxin suppresses the cell-mediated and humoral immune response to influenza A vims without affecting cytolytic activity in the lung., Toxicol. Sci., 56, 114, 2000. 

Figure 2. Human T cells, transduced with hdm2 81-88 epitope-specific and CD8 x A2Kb Tg mice-derived double-chain (Mu dc TCR 8-18) and non functional single-chain TCRs (Mu b 18 and sc TCR 3), were tested for cytolytic activity in response to (o) non-peptide o...

Exposure of lymphocytes to authentic N=0 did not induce a global inhibition of lymphocyte function. The cytolytic activity of alloactivated mouse splenocytes as well as a murine allospecific cytolytic T lymphocyte clone were unaffected by exposure to N=0 immediately prior to the cytotoxicity assay. Additionally, the motility of various lymphocyte populations, including Con A stimulated splenocytes, alloactivated mouse splenocytes, and a T lymphocyte clone were also unaffected by previous N=0 exposure (R. A. Hoffman, J. M. Langrehr, and R. L. Simmons, unpublished observations, 1994). Thus, brief exposure to -N=0 does not affect T lymphocyte microfilament-microtubule function nor the enzymes required to induce target cell destruction. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Holgate ST (1999) The epidemic of allergy and asthma. Nature 402(Suppl 6760) B2-B4 Hoskin DW, Reynolds T, Blay J (1994a) Colon adenocarcinoma cells inhibit anti-CD3-activated killer cell induction. Cancer Immunol Immunother CII 38(3) 201-207 Hoskin DW, Reynolds T, Blay J (1994b) Adenosine as a possible inhibitor of killer T-cell activation in the microenvironment of solid tumours. Int J Cancer 59(6) 854-855 Hoskin DW, Reynolds T, Blay J (1994c) 2-Chloroadenosine inhibits the MHC-unrestricted cytolytic activity of anti-CD3-activated killer cells evidence for the involvement of a non-Aj/ A2 cell-surface adenosine receptor. Cell Immunol 159(1) 85—93 Hoskin DW, Buttler JJ, Drapeau D, Haeryfar SM, Blay J (2002) Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells. Int J Cancer 99(3) 386—395... 

IFN-y also induces the costimulatory molecules on the macrophages, which increases cell-mediated immunity. As a consequence, there is activation and increase in the tumoricidal and antimicrobial activity of mononuclear phagocytes, granulocytes and NK cells. The activation of neutrophils by IFN-y includes an increase in their respiratory burst. IFN-y stimulates the cytolytic activity of NK cells. It is an activator of vascular endothelial cells, promoting CD4+ T lymphocyte adhesion and morphological alterations, which facilitates lymphocyte extravasation. IFN-y promotes opsonization by stimulating the production of IgG subclasses that activate the complement pathway. A summary of the characteristics of selected cytokines is shown in Table 2.3. 

Shea and colleagues [109-111] added an exciting contribution to this field They created molecular imprints for the peptide melittin, the main component of bee venom, in polymer nanoparticles, resulting in artificial antibody mimics that can be used for the in vivo capture and neutralization of melittin. Melittin is a peptide comprising 26 amino acids which is toxic because of its cytolytic activity. Shea and colleagues strategy was to synthesize cross-linked, acrylamide-based MIP nanoparticles by a process based on precipitation polymerization using a small amount of surfactant. To maximize the specificity and the affinity for melittin, a number of hydrophilic monomers were screened for complementarity with the template. The imprinted nanoparticles were able to bind selectively the peptide with an apparent dissociation constant of Ax>app > 1 nM [109]. 

Grisham MB, Jefferson MM, Melton DF, Thomas EL (1984) Chlorination of Endogenous Amines by Isolated Neutrophils. Ammonia-Dependent Bactericidal, Cytotoxic, and Cytolytic Activities of the Chloramines. J Biol Chem 259 10404... 

G24. Grisham, M. B., Jefferson, M. M., Melton, D. F., and Thomas, E. L., Chlorination of endogenous amines by isolated neutrophils. Ammonia-dependent bactericidal, cytotoxic, and cytolytic activities of the chloramines. J. Biol. Chem, 259, 10404-10413 (1984). 

A number of other lines of evidence also suggested that there may be another mode-of-action for BTI poisoning by injection other than its known, general cytolytic activity (3,22-24). Using the appearance of cytosolic lactate dehydrogenase (LDH) in insect hemolymph post-injection as a marker for cytotoxicity (36-37), we found that dissolved BTI 6-endotoxin was a potent cytotoxin. When T. ni, however, were injected with dissolved BTI 5-endotoxin and then incubated at 28, 15, and 9°, there was an increase in the LD50 with a decrease in temperature (Figure 2) but the LDH levels at 3.5 PPM BTI were unaffected by temperature. 

Moniewska A, Szyba K, Jazwiec B, et al. 1989. Chrysotile A affects YAC-1 cytolytic activity of spleen cells. Arch Imm Et Therap 37 61-68. 

Goldfarb R. H., Albertsson R, Nannmark U. and Kitson R. P. (1998). Cytolytic activities of IL-2 activated NK cells from MMTV/v-Ha-ras transgenic oncomice during tumor progression. In Vivo 12, 589-592. 

Grailer A, Sollinger HW Burlingham WJ (1988) A rapid assay for measuring both colony size and cytolytic activity of limiting dilution microcultures. Journal of Immunological Methods 107 111-117. 

At present, there are no reports indicating a cytolytic activity of natural 3-AP monomers and oligomers, and it appears that the ability to permeabilize cells is closely associated with those 3-AP compounds... 

Activates CD4/CD8 I cells, B cells, macrophages and NK cells Enhances cytolytic activity of LAK and NK cells... 

TNF0 T cells (especially Tnl-type CD4 T cells and cytotoxic CD8 T cells) Enhances B cell proliferation Enhances fibroblast proliferation Cytotoxic for a wide variety of tumour cell lines Accounts for some of the cytolytic activity of T cells, NK cells and LAK cells... 

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