ECM (Extra-Cellular Matrix). Network of connective tissue,
which fills spaces between cells, provides strength, binds cells and
tissues together and links almost every cell in the body;
Acute Phase Proteins
(APPs)
Cytokines.
Proteins /glycoproteins expressed by most cells, including activated
ECs, mast cells and macrophages; used in cellular communication in
response to infection or trauma, modulate cell growth, development,
repair, fibrosis, inflammation, immunity and other processes to maintain
body in a steady state;
Inflammatory Cytokines - alarm-signaling cytokines are secreted
by many cell types including ECs, but mainly by local inflammatory
immune cells (e.g. neutrophil granulocytes, macrophages) into the
bloodstream; include interleukins IL-1α, IL-1β, IL-6, tumor
necrosis factor TNF-α,
interferon-γ
INF-γ,
TGF-β?IL-1 and TNF-αhelp recruit/activate WBCs and other inflammatory
cells and increase vascular permeability within injured tissues, and
help induce fever /decreased appetite.
Anti-inflammatory Cytokines -
include IL-4, IL-6, IL-10, transforming
growth factor TGF-β(affects cell
proliferation);
Chemotactic Cytokines (Chemokines) -recruit monocytes to
sites of tissue injury and infection; include
IL-8, and monocyte chemotactic
proteins MCP-1and,
MCP-2;
Cytokines trigger synthesis and degradation of ECM: IL-6
increases plasma fibrinogen levels,
IL-1,
TNF-a,and TGF-Bdecrease them.
Acute-phase reactants (APRs).
Most produced by liver (some by other cell types, including monocytes, ECs, fibroblasts and
adipocytes)in response to
cytokines:
Some APRs increase during inflammation
(called positive APRs) - for example:
CRP
(C-reactive protein) - not normally present in blood, a reliable
risk-marker of inflammation/atherosclerosis;
- activates
the complement system (immune system defense mechanism) to opsonize (add
a negatively charged coating to) microbes in preparation for their
destruction;
- Enhances phagocytosis of low-density
lipoprotein, leading to the formation of foam cells;
- Data suggests CRP may increase CAMexpression;
Complement factors
-
complex series of protein molecules circulate in the plasma and other
extracellular fluids in an inactive form. Enzymes convert complements
into biologically active molecules when exposed to microorganisms or
other foreign substances to destroy or mark cells for destruction
Fibrinogen, prothrombin, plasminogen-
coagulation factors.
Other APRs decrease during inflammation
(called negative APRs) - E.g. albumin, transferrin.
MMP-9.
Matrix metallopeptidase-9 is one of the
matrix metalloproteinase enzymes that degrade ECM proteins and
can degrade the fibrous cap on plaque.;
MMP-9
digests ECM
decorin, elastin, fibrillin, laminin,
gelatin (denatured collagen), and collagen types IV, V, XI and XVI;
MMP-9 levels are elevated during inflammation in CHD, arthritis,
pulmonary-emphysema, diabetic retinopathy;
WBCs.
Immune system (IS) White Blood Cells (aka
leukocytes); provide action against infection or injury;
Neutrophils. Members of granulocytic polymorphonuclear cell (PMN) family (includes
basophils and eosophils); also release useful protein granules in a
process called degranulation.\
Phagocytes.
Neutrophils, monocytes and macrophages; ingest/destroy micro-organisms,
cellular debris, dead cells
Lymphocytes.
Small adaptive IS T-cells and B cells), large granular, innate IS
NK-cells.
Mast cell.
Immunoglobilin-E (Ig-E)-primed mast
cells resident in connective and mucosal tissues, locally release:
(a)
(from granules) histamine, anticoagulant heparin, serine proteases,
(b)
Eicosonoids PGD2 and LTC4,
(c)
Cytokines
(MPO), which can oxidize LDL
in the space just below the endothelium.
CAM (Cell surface Adhesion
Molecule). Enables a cell to adhere to
other cells or molecules in the ECM; specifically promotes adherence of
WBCs (e.g. monocytes) to endothelium; includes Intercellular CAM-1
(ICAM-1), Vascular CAM-1 (VCAM-1), E-Selectin
Fibroblasts.
Connective tissue cells that secrete precursors of all ECM
components.
Oxidative stress.
A situation where reactive oxidants
Reactive oxygen species (ROS) and
Reactive Nitrogen Species (RNS)(e.g. free radicals) can cause damage to cells if there are
insufficient antioxidants to control
them.
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