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 tissue injury or infection. Following the initial vascular changes, this phase ensures effective immune cell migration, activation, and function at the affected site to eliminate pathogens and initiate tissue repair.

Leukocyte Recruitment Cascade

Leukocyte recruitment happens in four steps: margination, adhesion, transmigration, and chemotaxis. Reduced blood flow causes leukocytes to move toward the vessel wall (margination) and to loosely bind to endothelial selectins, leading to rolling. During firm adhesion, leukocyte integrins (e.g., LFA-1, Mac-1) bind to endothelial adhesion molecules such as ICAM-1 and VCAM-1. This anchoring halts the rolling motion and prepares the cells for tissue entry.

In transmigration (diapedesis), leukocytes pass through endothelial junctions, aided by molecules such as PECAM-1 (CD31).

Once in the interstitial space, leukocytes respond to chemoattractants and migrate in a directed manner, a process known as chemotaxis. Key chemotactic agents include interleukin-8 (IL-8), complement component C5a, and leukotriene B4 (LTB4), which guide leukocytes to the precise site of injury.

Phagocytosis and Resolution

At the site, neutrophils perform phagocytosis, engulfing microbes or debris into phagosomes that fuse with lysosomes to form phagolysosomes. Reactive oxygen species and enzymes destroy pathogens. Afterward, neutrophils undergo apoptosis. Released enzymes may damage nearby tissue, potentially worsening inflammation. If the cause is eliminated, inflammation resolves and repair begins; if not, it may progress to chronic inflammation.