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Acute Inflammation II: Cellular Phase
The cellular phase of acute inflammation is a tightly orchestrated sequence of events that recruits leukocytes, primarily neutrophils, to sites of tis…
The cellular phase of acute inflammation involves steps that recruit leukocytes to the injury site.
First is margination, where leukocytes move toward the vessel wall as blood flow slows and viscosity increases. This is followed by rolling, where they loosely bind and unbind to endothelial selectins.
Next, during firm adhesion, leukocyte integrins bind tightly to endothelial adhesion molecules such as ICAM-1 and VCAM-1.
Then, in diapedesis, leukocytes squeeze between endothelial cells to enter the tissue.
Inside the phagolysosome, pathogens are broken down by reactive oxygen species and proteolytic enzymes.
After completing their role, neutrophils undergo apoptosis and are normally cleared quietly by macrophages.
If clearance is delayed, their enzymes may leak into the surrounding tissue and continue the inflammatory process.
If the injurious stimulus is eliminated, anti-inflammatory signals and pro-resolving mediators restore tissue homeostasis.
Persistent or unresolved inflammation can transition into chronic inflammation.
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Q1: What is margination in the cellular phase of acute inflammation?
Margination is the first step of leukocyte recruitment where reduced blood flow causes leukocytes to move toward the vessel wall as blood viscosity increases. This positioning along the endothelium prepares cells for the subsequent rolling and adhesion phases, enabling their eventual migration into inflamed tissue.
Q2: How do leukocytes move from rolling to firm adhesion?
During rolling, leukocytes loosely bind and unbind to endothelial selectins. Firm adhesion occurs when leukocyte integrins such as LFA-1 and Mac-1 bind tightly to endothelial adhesion molecules like ICAM-1 and VCAM-1. This tight binding halts rolling motion and anchors cells in preparation for tissue entry through diapedesis.
Q3: What happens during diapedesis in acute inflammation?
Diapedesis is the process where leukocytes squeeze between endothelial cells to enter tissue. Molecules such as PECAM-1 facilitate this transmigration. Once in the interstitial space, leukocytes respond to chemoattractants including IL-8, C5a, and leukotriene B4, which guide them to the precise injury site.
Q4: How do neutrophils destroy pathogens inside phagolysosomes?
Neutrophils engulf pathogens into phagosomes that fuse with lysosomes to form phagolysosomes. Inside, reactive oxygen species and proteolytic enzymes break down and destroy the pathogens. After completing their antimicrobial role, neutrophils undergo apoptosis and autophagy, then are normally cleared quietly by macrophages.
Q5: What causes tissue damage when neutrophil clearance is delayed?
If macrophage clearance of apoptotic neutrophils is delayed, neutrophil enzymes may leak into surrounding tissue and continue the inflammatory process, causing additional damage. This enzyme release extends inflammation beyond its intended protective role and can worsen tissue injury at the inflammation site.
Q6: How does acute inflammation resolve when the injury is eliminated?
When the injurious stimulus is eliminated, anti-inflammatory signals and pro-resolving mediators restore tissue homeostasis, allowing inflammation to resolve. If the cause persists or inflammation remains unresolved, it may transition into chronic inflammation, requiring different immune mechanisms for resolution and management.
Q7: What is the role of chemotaxis in leukocyte recruitment?
Chemotaxis is the directed migration of leukocytes in response to chemoattractants released at injury sites. Key chemotactic agents include interleukin-8, complement component C5a, and leukotriene B4. These chemical signals guide neutrophils and other leukocytes precisely to the location of tissue damage or infection.