regulation of respiratory burst involved in inflammatory response

Definition

Target type: biologicalprocess

Any process that modulates the rate, frequency or extent of a phase of elevated metabolic activity, during which oxygen consumption increases made as a defense response ; this leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals. [GOC:BHF, GOC:dph, GOC:rl, GOC:tb]

The respiratory burst is a crucial process in the inflammatory response, involving a rapid and transient increase in oxygen consumption by phagocytic cells, primarily neutrophils and macrophages. This burst leads to the production of reactive oxygen species (ROS), potent antimicrobial agents that play a critical role in the elimination of invading pathogens.

**Regulation of Respiratory Burst:**

1. **Activation of Phagocytic Cells:** The process begins with the activation of phagocytic cells by various stimuli, such as pathogen-associated molecular patterns (PAMPs) like lipopolysaccharides (LPS) on bacteria, or damage-associated molecular patterns (DAMPs) released from damaged tissues. These stimuli bind to specific pattern recognition receptors (PRRs) on the phagocyte surface, triggering intracellular signaling cascades.

2. **Signal Transduction:** Activation of PRRs activates a complex signaling pathway involving various kinases and adapter proteins. This pathway leads to the recruitment and activation of the NADPH oxidase complex, a multi-protein enzyme crucial for ROS production.

3. **NADPH Oxidase Assembly and Activation:** The NADPH oxidase complex is composed of several subunits, including cytosolic proteins (p47phox, p67phox, p40phox) and membrane-bound proteins (gp91phox, p22phox). Upon activation, these subunits translocate to the phagosomal membrane, where they assemble to form the active NADPH oxidase enzyme.

4. **Superoxide Production:** The assembled NADPH oxidase utilizes NADPH as a substrate and catalyzes the reduction of molecular oxygen (O2) to superoxide radical (O2-), the primary ROS produced during the respiratory burst.

5. **ROS Generation and Antimicrobial Action:** The superoxide anion is highly reactive and can directly damage microbial membranes and DNA. It also serves as a precursor for other potent ROS, such as hydrogen peroxide (H2O2) and hydroxyl radicals (OH-) generated through enzymatic and non-enzymatic reactions. These ROS collectively contribute to the antimicrobial activity of phagocytes.

6. **Regulation and Termination:** The respiratory burst is tightly regulated to prevent excessive ROS production and potential damage to host tissues. Negative feedback mechanisms involve various signaling pathways and molecules, including the production of anti-oxidants and the degradation of NADPH oxidase components.

**In summary, the regulation of the respiratory burst involves a complex interplay of signaling pathways, protein activation, and enzymatic reactions leading to the generation of ROS, which are essential for the antimicrobial activity of phagocytes in the inflammatory response.**'
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Proteins (1)

Compounds (18)