General characteristics and process dynamics
Plasma inflammatory mediators represent a complex of biologically active substances. They exist in the bloodstream as inactive precursors, are activated by specific activators, and are strictly controlled by inhibitors. The main feature of this group is functioning via a cascade mechanism, where the activation of one molecule triggers a chain reaction involving subsequent components.
In the dynamics of the inflammatory process, plasma factors do not come into play immediately. The strict sequence is as follows: first, cellular mediators are released in the tissues, provoking the primary vascular reaction, and only then are plasma mediators engaged. This leads to a massive influx of exudate into the lesion.
The global goal of all these reactions boils down to three tasks: reliable demarcation of the injury focus, fixation of the pathogenic factor within it, and its ultimate destruction.
Basic effects of plasma systems:
- A sharp increase in the permeability of the microvasculature.
- Recruitment of monocytes and polymorphonuclear leukocytes to the lesion (chemotaxis).
- Stimulation of phagocytosis processes.
- Initiation of intravascular coagulation.
Kinin system
The components of this system originate from blood plasma and other body fluids. Key representatives include kinins (specifically kallidin and bradykinin), as well as the enzyme kallikrein.
- Bradykinin has a pronounced hypotensive effect (lowers blood pressure) and causes arteriolar dilation. It is responsible for the sensation of pain in the focus of inflammation. In addition, it dramatically increases vascular permeability, stimulates collagenogenesis, and activates the enzyme cyclooxygenase.
- Kallikrein plays a crucial linking role. Its main significance lies in the activation of Hageman factor, which ensures the direct involvement of blood coagulation and fibrinolysis systems in the inflammatory process. Kallikrein also performs targeted leukocyte chemotaxis and stimulates phagocytes.
Complement system
The complement system consists of specific plasma proteins synthesized by hepatocytes, monocytes, and leukocytes. The main function of complement is bactericidal activity and cytolysis, i.e., the direct destruction of bacteria and cells (including the lysis of damaged host tissues).
Key components of the system, primarily the C3b and C5b fractions, cause a number of effects:
- Potent opsonization (preparing foreign particles for phagocytic uptake).
- Enhancement of chemotactic activity and adhesion of macrophages, neutrophils, and other leukocytes.
- Dilation of the capillary network and a significant increase in microvascular permeability.
- Additional stimulation of lipoxygenase and cyclooxygenase enzymes.
- Activation of Hageman factor, which again demonstrates the close interconnection of all three plasma systems.
Hemostasis system and Hageman factor
Components of the blood coagulation system are produced in the liver. During inflammation, the hemostasis system becomes an integral component rather than merely a mechanism for stopping bleeding.
The central link here is Hageman factor. It initiates blood coagulation and acts as a potent inflammatory mediator:
- Activates other plasma mediators (including the kinin system).
- Increases vascular wall permeability.
- Enhances neutrophil migration into the lesion.
- Stimulates platelet aggregation.
As a result of hemostasis system activity, microthrombi are formed, which physically block the spread of infection. Subsequently, fibrin clot lysis is triggered, leukocyte adhesion is enhanced, and fibroblast proliferation begins, preparing the tissue for regeneration.
Briefly: answers to topical questions
Which components form the plasma kinin system?
The plasma kinin system is formed by precursor proteins, enzymes, and active peptides.
- Kininogen is a high-molecular-weight precursor protein produced in the liver and circulating in the blood.
- Prekallikrein is an inactive precursor converted into its active form by blood clotting factor XII.
- Kallikrein is a trypsin-like serine peptidase that cleaves kinins from kininogen.
- Kinins (bradykinin, kallidin) are active peptides that cause arteriolar dilation, pain sensation, and increased microvascular permeability.
What are the pathways of complement system activation?
There are three main pathways of complement system activation:
- classical;
- lectin;
- alternative.
All three pathways converge at the stage of enzymatic complex formation—convertases—and culminate in the assembly of the membrane attack complex on the target cell surface.
Which inhibitors control the activity of plasma inflammatory mediators?
The activity of plasma inflammatory mediators is controlled by specific inhibitors of the complement, hemostasis, and fibrinolysis systems.
- C1 inhibitor (C1INH) — suppresses the esterase activity of classical and lectin pathway factors.
- Factor H (CFH) — the main regulatory protein of the alternative complement pathway.
- CD55 (DAF) — a glycoprotein regulating C3 convertase activity.
- CD59 (MIRL) — an inhibitor blocking membrane attack complex assembly.
- Antithrombin III — inhibits thrombin and blood clotting factors.
- Plasmin inhibitors — limit the action of plasmin in the fibrinolysis system.
Which blood clotting factors, besides Hageman factor, act as inflammatory mediators?
Besides Hageman factor, thrombin is an important inflammatory mediator from the blood coagulation system.
- Thrombin is an enzyme formed during hemostasis activation. In the focus of inflammation, it increases vascular endothelial permeability, stimulates the further release of biologically active substances from mast cells, and promotes the generation of the pro-inflammatory complement component C5a (anaphylatoxin).
The three plasma mediator systems are easy to remember with the three Ks rule: Kinins (pain and vessels), Komplement (lysis and opsonization), Koagulation (clots and Hageman factor).
Class and exam questions
In what sequence are mediators involved in the inflammatory process?
Inflammation always begins with the release of cellular mediators, which trigger the primary vascular reaction. Only after this are plasma mediators activated, ensuring the escape of exudate into the tissues.
What is the role of the complement system in inflammation?
Complement is responsible for cytolysis (destruction of bacteria and damaged host cells), opsonization of pathogens for phagocytic uptake, and leukocyte chemotaxis.
How does the hemostatic system help combat the damaging factor?
It forms microthrombi that physically demarcate the focus of inflammation and prevent the pathogen from spreading. Later, fibrin lysis and fibroblast proliferation occur for healing.
Which substance causes pain during inflammation?
The main pain mediator of plasma origin is bradykinin, which belongs to the kallikrein-kinin system.
What else to study on this topic
- Mechanisms of Hageman factor activation and inhibition
- Role of complement fractions C3b and C5b in opsonization processes
- Interaction of kallikrein with the coagulation and fibrinolysis systems
- Effect of plasma mediators on cyclooxygenase and lipoxygenase enzymes
- Process of intravascular coagulation as a component of the inflammatory response
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