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GSE Inflammation Process

Meet “The players” in the inflammatory process

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 CAM expression;

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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