Biology Reference
In-Depth Information
factors further activate mononuclear and PMN phagocytes.
Unfortunately, several of the produced microcidal agents tend to leak out
and cause the severe damage of the surrounding endothelia and
vasculature that is often seen in sepsis patients. Blood pressure also
decreases with infection as the result of the up-regulation of nitric oxide
synthase. These symptoms and others such as fever, coagulation
disorders, microthrombi, and myocardial depression may result in
multiple organ failure and finally lead to septic shock.
In order to maintain homeostasis, anti-inflammatory cytokines also
are released; interleukin-4, interleukin-10, interleukin-13, and
transforming growth factor-β, as well as natural cytokine inhibitors that
includes soluble TNF receptors, IL-1 receptor antagonist, and soluble
IL-1 receptors (Cavaillon, 2003).
In addition, liver parenchymal cells
produce acute-phase proteins such as C-reactive protein, serum amyloids
(A and P), hemopexin, haptoglobin, complement C3 and C9, α
1
-acid
glycoprotein, α
2
-macroglobulin, and proteinase inhibitors to ameliorate
the damaged caused by the inflammatory response (Fey
et al.
, 1994,
Schumann and Zweigner, 1999, Steel and Whitehead, 1994, Kuipers
et
al.
, 1994, Ramadori
et al.
, 1990).
6.1.3.4
Role of LPBP, CD14, Tlr4, and other proteins
In humans, there is a highly developed pathogen recognition immune
system. In particular, several bacterial products are recognized as
xenobiotic including foreign DNA and RNA, lipoproteins, flagellin,
zymosan, peptidoglycan, and, of course, LPS. The pathogen-associated
molecular patterns are recognized by a group of at least ten membrane
receptors called toll-like receptors (TLRs). Among these receptors is
TLR4, a 92 kDa protein (841 amino acids), that is partly responsible for
recognizing LPS via the lipid A binding site (Fig. 6.4). TLR4 also binds
several other foreign ligands including pneumolysin from
Streptococcus
pneumoniae
, respiratory syncytial virus (RSV) coat protein, teichuronic
acids, bacterial heat shock protein (Hsp) 60, as well as host-born ligands
such as lung surfactant protein A, hyaluronin oligosaccharides, heparan
sulfate, and fibrinogen fragments (Rossignol and Lynn, 2005). TLR4-
deficient mice (C3H/HeJ) are hypo-responsive to the effects of LPS, an
