Which complement fragment is the most potent anaphylatoxin and primary chemotactic agent in acute inflammation?

Explanation

## Complement Anaphylatoxins and Chemotaxis **Key Point:** C5a is the **most potent anaphylatoxin** and the **primary chemotactic agent** in the complement cascade. It is 100–1000 times more potent than C3a in inducing mast cell degranulation and leukocyte recruitment. ### Hierarchy of Anaphylatoxin Potency | Fragment | Anaphylatoxin Potency | Chemotactic Potency | Mast Cell Degranulation | |----------|----------------------|-------------------|------------------------| | C5a | Very high (most potent) | Very high (most potent) | Strongest | | C3a | Moderate | Weak | Moderate | | C4a | Minimal | Minimal | Minimal | | C2a | None | None | None | **High-Yield:** C5a is generated from C5 cleavage during all three complement pathways (classical, alternative, and lectin). It acts on **C5a receptors (C5aR1 and C5aR2)** on mast cells, neutrophils, and macrophages. ### Biological Effects of C5a 1. **Mast cell and basophil degranulation** → histamine release → increased vascular permeability 2. **Neutrophil chemotaxis and activation** → migration to inflammatory site 3. **Opsonization enhancement** → C3b deposition on pathogens 4. **Smooth muscle contraction** → bronchospasm (in severe reactions) 5. **Increased vascular permeability** → exudation **Mnemonic:** **C5a = "5-Star Chemotactic Agent"** — remember that C5a is the most important complement fragment for leukocyte recruitment and systemic inflammation. **Clinical Pearl:** In sepsis and acute respiratory distress syndrome (ARDS), excessive C5a generation contributes to systemic inflammation and multi-organ failure. C5a inhibitors (e.g., eculizumab) are used in complement-mediated diseases like atypical hemolytic uremic syndrome (aHUS). **Warning:** Do not confuse C5a with C5b. C5b is part of the **membrane attack complex (MAC)** and is NOT an anaphylatoxin; it has no chemotactic activity.