Lytic function

Lytic growth of Mu can occur either upon initial infection, if the c gene repressor is not formed, or by induction of a lysogen. In either case, replication of Mu DNA involves repeated transposition of Mu to multiple sites on the host genome. Initially, transcription of only the early genes of Mu occurs, but after gene C protein, a positive activator of late RNA synthesis, is expressed, the synthesis of the Mu head and tail proteins occurs. Eventually, expression of the lytic function occurs and mature phage particles are released. 

Raskovalova T, Huang X, Sitkovsky M, Zacharia LC, Jackson EK, Gorelik E (2005) Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells. J Immunol 175(7) 4383—4391... 

The biocatalyst a-chymotrypsin s ability to hydrolyze 20 is inhibited in the presence of copolymer 19a loaded with 0.2 mol% of the triphenyl carbinol units. 47b Photoirradiation of 19a results in heterolytic bond cleavage and the formation of the cationic copolymer 19b. In this polymer structure, the biocatalyzed hydrolysis of 20 is activated (V = 1.0 pM min-1). The polymer-induced photostimulated activation and deactivation of a-chymotrypsin in the different membrane environments correlates with the permeability and transport properties of the substrate 20 through the different structures of the polymer membranes.1471 Flow dialysis experiments showed that the polymer states 17a, 18a, and 19a are nonpermeable to 20, and hence the biocata-lytic functions of the immobilized enzyme are blocked. The polymer structures 17b,... 

We have shown that TBTs, DBTs, TPTs, and TMTs, as well as other OTs, can significantly reduce the lytic function of human natural killer cells." Thus, OTs may promote cancer development and viral infection in humans, due to their capacity to interfere with the ability of NK cells to lyse their targets. This chapter is a summary of studies examining the effects of several OTs on the function of human NK cells. These include the effects of the various OTs on lytic function, ability to bind to target cells, intra-cellular ATP levels, and the functions of enzymes (MAPKs) that are critical to the lytic function of NK cells. 

Table 4.5.1 Effects of tri-n-butyltin chloride on the lytic function, binding function, ATP levels, CD16 levels, CD56 levels, granzyme B levels, and perforin levels of human NK cells ...

Exposure of NK cells to 300 and 500 nM TBTC for 1 h produces significant decreases in their lytic function (Table 4.5.1)7 A concentration of 300 nM TBTC decreased lytic function by 36%, while 500 nM cansed abont an 80% decrease in this function. NK cells exposed to TBTC for 24 h showed significant decreases in lytic function at 25-200 nM TBTC (Table 4.5.1), with 200 nM TBTC cansing a greater than 90% loss of lytic function and 100 nM causing about a 60% decrease. Decreases in lytic... 

The results from these studies indicate that TBTC exposures can result in decreases in ATP levels. However, TBTC-induced decreases in lytic function do not show a significant association with decreased ATP levels, except after 48 h and 6 days. These results indicate that the loss of lytic function induced by exposures to TBTC cannot be accounted for solely by TBTC-induced decreases in ATP levels. 

The effects of TMTC exposures on the lytic function of NK cells are summarized in Table 4.5.4. Exposure of NK cells to TMTC for 1 h caused no significant decreases in cytotoxic function at any concentration. After 24 h, 10 pM TMTC caused a very significant decrease (76%) in the capacity of NK cells to lyse tumor cells. A 48 h exposure decreased the ability of NK cells to lyse tumor cells at concentrations as low as 2.5 pM (23%). A 6 d exposure to 5 pM TMTC caused a very significant loss of cytotoxic function (96%). i... 

Effects of Methyldiphenyltin Chloride (MDPTC) on Human NK Cell Function Effects on Lytic Function... 

In contrast to TMTC and DMPTC, exposure of NK cells to MDPTC for 1 h caused very significant decreases in NK lytic function at both 5 and 2.5 pM (Table 4.5.6). Exposure to 200 and 100 nM MDPTC... 

Table 4.5.5 Effects of dimethylphenyltin chloride on the lytic function and binding function of human NKcells ...

In order for NK cells to lyse their targets, including tumor cells, the NK cell must bind to the target utilizing cell surface proteins present on the NK cell, as well as on the target. We found that each of the OTs is able to decrease the ability of NK cells to bind to their targets. However, this decrease is a slower consequence of OT exposure than is the decrease in lytic function. 

One consequence of NK cell exposure to OT that occurs quickly (within 10 minutes) is an increase in the activation of mitogen-activated protein kinases (MAPK). These enzymes are critical to the function of the NK cells, as well as nearly all other cell types. TBTC can significantly activate MAPKs within 10 min of exposure and this activation can be accounted for by TBTC-induced activation of the immediate upstream activators of MAPKs, referred to as MAPK kinases (MAP2Ks). Activation of MAPKs by TBTC would leave the NK cell unable to respond to target cells when they were encountered. The activation of the MAPK pathway by OT exposure occurs within a timeframe that could account for the loss of lytic function seen at exposures of less than 48 h, while the other alterations such as ATP decreases and binding decreases take longer to occur. We have unpublished data indicating that DBTC is also able to increase MAPK activity in NK cells within 10 min. Thus, it will be important to examine the other OTs to determine if this is a common mechanism in the OT-induced inhibition of NK lytic function. 

Finally, a series of OTs that differed in their lipophilicity (TMTC, DMPTC, MDPTC, and TPTC) has been shown to decrease the lytic function of NK cells in the order TMTC[Pg.479]

Head Tail Replaceable region Lytic functions ... 

Most of the prophage genes are repressed and their lytic functions remain dormant, but certain agents that interfere with DNA replication in the host may, at a later date, cause the viral DNA to be excised from the bacterial chromosome. It can then become virulent, reproduce and cause lysis of the cell. 

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