Biology Reference
In-Depth Information
relative risk of 1.90 compared to whites). Sepsis is most dangerous in
black men, the elderly, immuno-compromised individuals, and in
critically ill patients.
Before 1987, Gram-negative bacterial infections were the principal
cause of sepsis, but in more recent years, this role has been overtaken by
Gram-positive bacteria. In 2000, Gram-positive bacteria accounted for
52.1 percent, Gram-negative bacteria 37.6 percent, polymicrobial origins
4.7 percent, fungi 4.6 percent, and anaerobes 1.0 percent of all cases
(Martin
et al.
, 2003). The organs that failed the most frequently were the
lungs (18%), followed by the kidneys (15%), and then cardiovascular
(7%), hematological (6%), metabolic (4%), and neurological failure
(2%). At present, there is no effective treatment for severe sepsis
(Shiozaki
et al.
, 2006).
6.1.2 Lipoteichoic acid, peptidoglycan, and exotoxins
Unlike Gram-negative bacteria, Gram-positive bacteria have a number of
active components that promote an immunological response, including
lipoteichoic acid (LTA), peptidoglycan (PGN), and exotoxins. Compared
to LPS, much less is known about these components of Gram-positive
bacteria. LTA and PGNs, similarly to LPS, induce the release of TNFα,
interleukin-1 (IL-1), IL-6, INF-γ, and nitric oxide from macrophages,
monocytes, and several other cells (Bhakdi
et al.
, 1991, Keller
et al.
,
1992, Kengatharan
et al.
, 1996, Wang
et al.
, 2000). LTA (
3
), which
resembles LPS in many aspects, is a glycolipid made up of a
diacylglycerol lipid portion and an unbranched chain of repeating units
of polyglycerophosphate that is bound to a hexapyranosyl sugar (Fig.
6.2). As with LPS, differences in the acyl chain length are observed
among different bacterial species. The immunological potency of LTA is
highly dependent on the bacterial species. PGN consists of a tetrapeptide
portion of
L
-alanine,
D
-glutamine,
L
-lysine, and
D
-alanine, as well as a
glycan portion containing repeating disaccharide
N
-acetylmuramic acid-
(β1-4)-
N
-acetylglucosamine units (between 5 and 30). The short peptide
is cross-linked to the peptide portion of another chain by a pentaglycine
group to provide the molecular network that makes up the cell wall. The
