activation of plasma proteins involved in acute inflammatory response

Definition

Target type: biologicalprocess

Any process activating plasma proteins by proteolysis as part of an acute inflammatory response. [GOC:jal, ISBN:0781735149]

The acute inflammatory response is a complex biological process involving the activation of plasma proteins, primarily those of the complement system, coagulation cascade, and kinin system. These systems are normally inactive in the circulation but are rapidly activated upon tissue injury or infection.

**Complement System Activation:**

* **Classical Pathway:** Initiated by antigen-antibody complexes binding to C1q, leading to activation of C1r and C1s. C1s cleaves C4 and C2, generating the C4b2a complex (C3 convertase).
* **Lectin Pathway:** Mannose-binding lectin (MBL) binds to mannose residues on microbial surfaces, activating MASP-2, which cleaves C4 and C2, forming C4b2a.
* **Alternative Pathway:** Triggered by spontaneous hydrolysis of C3, generating C3(H2O). C3(H2O) binds to Factor B, which is cleaved by Factor D, forming C3bBb (alternative C3 convertase).
* **C3 Convertase Formation:** All pathways converge to form C3 convertase, which cleaves C3 into C3a and C3b.
* **C5 Convertase Formation:** C3b binds to C3 convertase, creating C5 convertase (C4b2a3b or C3bBb3b), which cleaves C5 into C5a and C5b.
* **Membrane Attack Complex (MAC) Formation:** C5b initiates the assembly of C6, C7, C8, and multiple C9 molecules, forming the MAC, which inserts into cell membranes, causing lysis.

**Coagulation Cascade Activation:**

* **Tissue Factor Pathway:** Initiated by exposure of tissue factor (TF) to blood, triggering the activation of factor VIIa, which in turn activates factor X.
* **Contact Pathway:** Initiated by contact of blood with negatively charged surfaces, leading to the activation of factor XII. Factor XIIa activates factor XI, which then activates factor IX.
* **Common Pathway:** Both pathways converge at factor X, leading to the activation of thrombin. Thrombin converts fibrinogen to fibrin, forming a clot that helps to stop bleeding and contain the infection.

**Kinin System Activation:**

* **Prekallikrein Activation:** Factor XIIa activates prekallikrein to kallikrein.
* **Bradykinin Generation:** Kallikrein cleaves high molecular weight kininogen (HMWK), generating bradykinin. Bradykinin is a potent vasodilator and mediator of pain and inflammation.

**Consequences of Plasma Protein Activation:**

* **Vasodilation:** Mediated by C3a, C5a, and bradykinin, leading to increased blood flow to the site of injury.
* **Increased Vascular Permeability:** C3a, C5a, and bradykinin increase the permeability of blood vessels, allowing fluid and immune cells to escape into the tissues.
* **Chemotaxis:** C5a and bradykinin attract neutrophils, macrophages, and other immune cells to the site of injury.
* **Opsonization:** C3b binds to microbes, marking them for phagocytosis by immune cells.
* **Inflammation Resolution:** After the inflammatory response is resolved, the activated plasma proteins are inactivated by regulatory proteins.

The activation of plasma proteins in the acute inflammatory response is a tightly regulated process that helps to control and resolve infection and tissue injury.'"

Proteins (1)

Compounds (39)