Spatiotemporal dynamics of complement C5a production within bacterial extracellular polymeric substance.
Spatiotemporal dynamics of complement C5a production within bacterial extracellular polymeric substance.
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DOI:
10.1159/000345705
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发表时间:
2013
影响因子:
5.3
通讯作者:
Younger JG
中科院分区:
文献类型:
--
作者:
Conrad EC;Hsu YY;Bortz DM;Younger JG
Opsonization and anaphylatoxin production are early events in innate response to bacterial pathogens. Opsonization alone is frequently not lethal and production of anaphylatoxins, especially C5a, allows for recruitment of cellular defenses. Complement biochemistry is extensively studied and computational models have been previously reported. However, a critical feature of complement mediated attack is its spatial dependence: diffusion of mediators into and away from a bacterium is central to understanding C5a generation. Spatial dependence is especially important in biofilms, where diffusion limitation is crucial to bacterial counterdefense. Here we develop a model of opsonization and C5a production in the presence of a common blood borne pathogen, Staphylococcus epidermidis. Our results indicate that when complement attacks a single cell, diffusion into the extracellular polymeric substance (EPS) is complete within 10 msec and that production of C5a peaks over the next 15 minutes. When longer diffusion lengths (as in an EPS-rich biofilm) are incorporated, diffusion limitation appears such that the intensity and duration of C5a production is increased. However, the amount of C5a produced under several likely clinical scenarios where single cells or sparse biofilms are present is below the kD of the C5a receptor suggesting that complement activation by a single bacterium may be difficult to detect when diffusion is taken into account.
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影响因子:
4.7
作者:
Laarman, Alexander;Milder, Fin;van Strijp, Jos;Rooijakkers, Suzan
通讯作者:
Rooijakkers, Suzan
DOI:
10.2119/molmed.2010.00149
发表时间:
2011-03
期刊:
Molecular medicine (Cambridge, Mass.)
影响因子:
--
作者:
Ehrnthaller C;Ignatius A;Gebhard F;Huber-Lang M
通讯作者:
Huber-Lang M
DOI:
10.1073/pnas.80.17.5430
发表时间:
1983-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
作者:
PANGBURN, MK;SCHREIBER, RD;MULLEREBERHARD, HJ
通讯作者:
MULLEREBERHARD, HJ
DOI:
10.1165/rcmb.2009-0292oc
发表时间:
2010-11-01
影响因子:
6.4
作者:
Nypaver, Christina M.;Thornton, Margaret M.;Younger, John G.
通讯作者:
Younger, John G.
影响因子:
3.1
作者:
Kozel, TR;Tabuni, A;Levitz, SM
通讯作者:
Levitz, SM