Microbicidal activity

DL-10 (35) T cell, fibroblast Suppression of B- and T-cell proliferation. Inhibition of LPS-induced monocyte IL-1, IL-8, and TNF production. Induction of IL-lra. Suppression of free radical release and NO-dependent microbicidal activity of macrophages. 

Lissner, C. R., Weinstein, D. L. and O Brien, A. D. (1985). Mouse chromosome 1 Ity locus regulates microbicidal activity of isolated peritoneal macrophages against a diverse group of intracellular and extracellular bacteria, J. Immunol., 135, 544-547. 

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

Lactoferrin is the major whey protein present in breast milk (Teraguchi et ah, 1996) with many microbicidal properties (Leon-Sicairos et ah, 2006). The concentration of lactoferrin in milk has been reported as 1 g/liter in mature milk and 7 g/liter in colostrum (Houghton et ah, 1985). The concentration of lactoferrin in breast milk is controlled by the reproductive hormones prolactin and estrogen (Ward et ah, 2005). Lactoferrin has been demonstrated to resist digestion in the infant gut as it has been recovered intact from the stool of breast-fed infants (Bemt and Walker, 1999). Lactoferrin acts mainly in an iron-free state (apo-lactoferrin) and its microbicidal activity is reported to increase in proportion to its concentration in milk (Leon-Sicairos et ah, 2006). 

Formation of the hydroxyl radical. Because the killing of certain microbes was dependent on the ability of PMNs to undergo the respiratory burst, the actual microbicidal species was sought. It had been shown that a potent oxidant was formed during the catalytic action of xanthine oxidase on xanthine an enzymic reaction which, like the PMN, produces both 07 and H2O2. This potent oxidant was proposed to be the hydroxyl radical formed by the reaction between O7 and H2O2 (reaction 4). Because such an oxidant seemed a likely candidate to mediate the microbicidal activity of PMNs, the formation of OH was assessed in PMNs. 

Thormar, et al. 1999. Hydrogels containing monocaprin have potent microbicidal activities against sexually transmitted viruses and bacteria in vitro. Sex Trans Infect 75 181. 

To prevent the problems caused by slime formation, various microbicides (slime-controlling agents) can be used. Of these, 5-chloro-2-methyl-4-isothiazo-line-3-one (Cl-MIT 1) is the most widely used as a slime-controlling agent, a bactericide, an algicide or a fungicide, for various industrial water systems such as those in cooling-water units or papermills, as it has an excellent microbicidal activity. [2]... 

Further to these results, the microbicidal activities of FIBCIDE-KF and KATHON WT were evaluated. The minimum inhibitory concentrations (MIC) for Pseudomonas aeruginosa, Pseudomonas putida, Bacillus subtilis and Microbacterium sp. are identical for both compounds, so the microbicidal effect has not diminished (Figure 10). It appears that the biocidal effects are similar because the Cl-MIT in the inclusion complex is released into water, as shown in Figure 6. 

It should be noted that the new biocide has an excellent microbicidal activity against Legionella pneumophila in cooling-water systems. [8]... 

Thorgeirsdottir, T. O., Thormar, H., and Kristmundsdottir, T. (2005), The influence of formulation variables on stability and microbicidal activity of monoglyceride monocaprin, /. Drug Deliv. Sci. Tech., 15, 233-236. 

Edema toxin does not produce major tissue damage. In fact, its major role is to impair phagocyte function (Leppla, 2000). This is consistent with other toxins which fimction to elevate cAMP concentrations. Edema toxin inhibits phagocytosis of spores by human PMNs (O Brien et al, 1985) similar to LF this is in contrast to spores which promote immune cell uptake (see Table 31.1). Increased intracellular cAMP induced by EF inhibits neutrophil chemotaxis, phagocytosis, superoxide production, and microbicidal activity (Crawford et al, 2006 Turk, 2007 O Brien et al, 1985 Friedman et al, 1987 O Dowd et al, 2004 Ahmed et al, 1995). EF has been shown to inhibit TNFa and increase IL-6 production (Hoover et al, 1994). Increased cAMP levels also block LPS-induced activation... 

The interferons are naturally protective substances. Type I IFNs are produced by most cells in response to viruses, bacteria or their products. For example, IFN-a and IFN- (3 are produced in response to viral infection and inhibit viral replication plus assist the induction of viral resistance. Not only do they possess antiviral activity but they also mediate the response to other infectious agents, demonstrate antitumor activity, and play a role in the regulation of growth, differentiation and development [211]. In contrast, IFN-y has more potent immunoregulatoiy effects than either IFN-a or -(3. Among its properties, IFN-y is capable of activating human macrophage oxidative metabolism and microbicidal activity. 

Therapeutically, cellulose acetate phthalate has recently been reported to exhibit experimental microbicidal activity against sexually transmitted disease pathogens, such as the HIV-1 retrovirus. 

IL-10 T cells Monocytes Macrophages Keratinocytes Activated B cells Inhibits cytokine secretion by ThI- and TH2-type I cell clones Impairs accessory function of macrophages and dendritic cells Inhibits cytokine secretion by macrophages (TNFa, IL-1, IL-6, IL-8, GM-CSF) and microbicidal activity Activates B cells (proliferation and secretion of igM, igG and IgA) Induces proliferation of thymocytes... 

Delta-9-THC is the main active constituent extracted from Cannabis sativa (Tuner, 1985 in Marijuana 1984, Ed. Harvey, DY, IRL Press, Oxford). Numerous articles have described not only psychotropic effects of cannabinoids but also their influence on the immune function [Hollister L. E., J. Psychoact. Drugs 24 (1992) 159-164]. The majority of in vitro studies have shown that cannabinoids have immunosuppressant effects inhibition of the mitogen induced proliferative responses of T lymphocytes and B lymphocytes [Luo, Y. D. et ah, Int. J. Immuno-pharmacol. (1992) 14,49-56 Schwartz, H. et at., J. Neuroimmunol. (1994) 55,107-115], inhibition of the activity of cytotoxic T cells [Klein et at., J. Toxicol. Environ. Health (1991) 32, 465-477], inhibition of the microbicidal activity of macrophages and of TNF-a synthesis [Arata, S. et at.. Life Sci. (1991) 49, 473-479 Fisher-Stenger et al., J. Pharm. Exp. Then (1993) 267, 1558-1565] and inhibition of the cytolytic activity and the TNFa production of large granular lymphoc3rtes [Kusher et al.. Cell. Immun. (1994) 154, 99-108],... 

De Sole P, Lippa S, Littarru GP. Whole blood chemiluminescence a new technical approach to assess oxygen dependent microbicidal activity of granulocytes, J Clin Lab Autom 1983 3 391-400. 

Suzuki, K., Tokoro, A., Okawa, Y., Suzuki, S., and Suzuki, M. 1985. Enhancing effects of A-acetyl chitoligosaccharides on the active oxygen-generating and microbicidal activities of peritoneal exudates cells in mice. Chem. Pharm. Bull. 33, 886-888. 

In contrast, IFN-y has more potent immunoregulatory effects than either IFN-a or -p. Among its properties, IFN-y is capable of activating human macrophage oxidative metabolism and microbicidal activity. 

Fig. 10.2-9 Protein Medicinal Chemistry. The N-terminus of the chemokine RANTES was systematically modified to improve receptor binding and HIV microbicide activity.

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