Guest guest Posted September 6, 2005 Report Share Posted September 6, 2005 Another group found otherwise, ie that all neutrophil granule antimicrobials killed Bb powerfully. I've been meaning to look into this discrepancy. > B. over there posted excerpts from the following study: > > Elastase Is the Only Human Neutrophil Granule Protein That Alone Is > Responsible for In Vitro Killing of Borrelia burgdorferi > > the study can be found here: > > http://iai.asm.org/cgi/content/full/66/4/1408 > > His post here: > > /message/82581 > > The following statement from the study grabbed my attention for a > different reason: > > " It was somewhat unexpected that among all granule proteins, only > elastase was found to kill B. burgdorferi in our experimental > conditions. This protein, which consists of 218 amino acid residues > and contains two asparagine-linked carbohydrate side chains " > > My spectra cell testing showed me deficient in asparagine (amino > acid). Another friend of mine, who also has chronic osteomyelitis, > also tested defecient in asparagine. > > penny Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 6, 2005 Report Share Posted September 6, 2005 Here's the entire closing discussion from the paper. If correct, it gives at least one good reason why targeting co-infections, rather than Bb alone, is a good idea, since what kills B.b doesn't kill e.coli, and vice versa. Also, I think I'll stop delaying and order that Asparagine, and some other amino acid/enzymes right away, since they seem to be helping get the job done against a lot of organisms, at least they were back in '98, when this paper was written. penny Discussion This work describes for the first time the identification and characterization of a B. burgdorferi-killing factor from the human neutrophil. The results demonstrate that (i) oxygen-independent mechanisms are active against these spirochetes, whereas the MPO- H2O2-Cl system is not effective in conditions in which E. coli is efficiently killed, and (ii) among all granule proteins, only elastase possesses Borrelia-killing activity on its own. This protein, while ineffective toward E. coli and S. faecalis, was found to be active against B. burgdorferi. The killing activity is independent of the proteolytic activity. Human neutrophils contain in their secretory granules a number of potentially cidal proteins such as cathepsin G, azurocidin, bactericidal permeability-increasing protein, proteinase 3, and defensins (9) which either on their own or, as in the case of MPO, in conjunction with oxygen metabolites (12) are active against different microorganisms. It was somewhat unexpected that among all granule proteins, only elastase was found to kill B. burgdorferi in our experimental conditions. This protein, which consists of 218 amino acid residues and contains two asparagine-linked carbohydrate side chains (28), is a trypsin-like proteolytic enzyme without a clear-cut independent antibacterial activity (6, 31). In fact, only extremely high, arguably nonphysiological concentrations have been reported to kill Capnocytophaga sputigena (17). Nonetheless, a helper role has been attributed to elastase, which appears to potentiate the cidal effect of other active proteins. This has been observed to be the case for the killing of C. sputigena, where very high concentrations of azurocidin become cidal when combined with elastase (18). Interestingly, the interaction between these two granule proteins was found to be enzyme dependent. Similarly, synergy between elastase and MPO or cathepsin G has been reported to result in the killing of E. coli and Staphylococcus aureus, but in this case the potentiating effect was unaffected by heating and therefore unrelated to the proteolytic activity of elastase (23). We found that elastase was borreliacidal on its own. This was independent from its proteolytic activity, in keeping with what has been reported for other members of the serprocidin family. In fact, cathepsin G kills S. aureus, S. faecalis, E. coli, Pseudomonas aeruginosa (22), and Acinetobacter sp. (30) even after being deprived of its enzymatic activity. Additionally, azurocidin is a killing protein yet is not proteolytic (32). This finding suggests that the cidal function of these proteins is unrelated to a degradative activity. Our results show that borreliae are very sensitive to elastase. In fact, concentrations of 3 to 5 µg/ml are sufficient to kill the microorganisms in the in vitro assay. These amounts are compatible with a physiological situation in which a very small proportion (<0.001%) of the total elastase content of the neutrophil (1.5 µg per 106 cells [8]) would be secreted into spirochete-containing phagocytic vacuoles (ca. 0.2 µm in diameter and 30 µm in length), assuming a minimum of one ingested microorganism per cell. Although we cannot exclude completely the possibility of a minor but very potent contaminant being responsible for the killing of borreliae, this seems unlikely in view of the fact that such a contaminant should have copurified with elastase, i.e., should be similar in molecular size and have the same charge characteristics. Regarding the possible borreliacidal mechanism of elastase, it may be associated to its interaction with some unknown component of the outer membrane of the spirochetes. This component would be present in both laboratory and freshly isolated, virulent strains, which we have observed to be equally susceptible to elastase (Table 4). Interactions at the level of the outer surface of the microorganisms can be lethal, as demonstrated by the fact that a monoclonal antibody to OspB has been found to be borreliacidal (7). It remains to be established whether elastase acts on borreliae through such a mechanism. http://iai.asm.org/cgi/content/full/66/4/1408 Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 6, 2005 Report Share Posted September 6, 2005 I kind of figured that. I hope you do look into it. I'm still ordering that Asparagine, because my guess is that mine's being depleted from its fight against whichever bugs I've got (since it seems to work against a number of the ones I know I've got). Very little out there on this " non-essential " amino acid, but out of all the amino acids tested, interesting that this one would show deficient in both me and my friend who have the same infection. penny > > B. over there posted excerpts from the following study: > > > > Elastase Is the Only Human Neutrophil Granule Protein That Alone > Is > > Responsible for In Vitro Killing of Borrelia burgdorferi > > > > the study can be found here: > > > > http://iai.asm.org/cgi/content/full/66/4/1408 > > > > His post here: > > > > > /message/82581 > > > > The following statement from the study grabbed my attention for a > > different reason: > > > > " It was somewhat unexpected that among all granule proteins, only > > elastase was found to kill B. burgdorferi in our experimental > > conditions. This protein, which consists of 218 amino acid residues > > and contains two asparagine-linked carbohydrate side chains " > > > > My spectra cell testing showed me deficient in asparagine (amino > > acid). Another friend of mine, who also has chronic osteomyelitis, > > also tested defecient in asparagine. > > > > penny Quote Link to comment Share on other sites More sharing options...
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