Chemotaxis and Triggering Factors
The process begins with chemotaxis — the directed movement of phagocytes and mediator-producing cells into the site of injury driven by chemoattractants. These signals include immunoglobulins, C-reactive protein, cytokines (IL-1, IL-8, TNF-α), complement system fragments (C5a, C3a), as well as microorganisms and their toxins. Lipid mediators (leukotriene B4, thromboxane A2), bradykinin, cationic proteins, immune complexes, and products of fibrin and collagen degradation also play key roles.
The release of mediators follows a strictly regulated sequence:
- Immediately following tissue injury, the tissue releases kinins, thrombin, and proserinesterases. Activation of the latter initiates a cascade of molecular conversions.
- As blood vessels become involved, fibrinogen and the complement system are activated.
As a result, basophils, eosinophils, monocytes, platelets, mast cells, and APUD system cells are recruited to the focus. Resident macrophages simultaneously produce cytokines, amplifying chemoattraction.
Margination and Adhesion
Leukocyte extravasation begins with margination. As blood flow slows down (stasis), white blood cells move out of the central axial column toward the endothelial lining.
Normally, both the endothelium and leukocytes carry a net negative charge and thus repel each other. During inflammation, plasma cations ($Ca^{2+}$, $Mn^{2+}$, $Mg^{2+}$) alter the endothelial surface charge, facilitating physical attraction of negatively charged leukocytes.
This is followed by molecular adhesion. Leukocytes enter an activated state and upregulate adhesion molecules in response to interleukins, leukotriene B4, interferon-α, TNF-α, and bacterial lipopolysaccharides. Complement fragments (C5a, C1, C3) and IgG Fc fragments further promote adherence. Endothelial cells, in turn, express integrins and intercellular adhesion molecules (ICAM-1, VCAM-1).
Diapedesis (Transmigration)
Once anchored to the vessel wall, the leukocyte begins its migration into the tissue, known as diapedesis (transmigration). Leukocyte-derived enzymes induce contraction of endothelial cells, widening interendothelial junctions.
- The neutrophil adheres tightly to the endothelium.
- The cell extends a pseudopodium that squeezes through the interendothelial gap. Electron microscopy shows that the cell nucleus remains well-defined during this stage.
- The leukocyte squeezes through into the space between the endothelium and the basement membrane.
- The basement membrane undergoes localized enzymatic degradation, allowing the cell to enter the inflammatory site (collagen fibers become visible behind the membrane on micrographs).
This mechanism is universal for all formed blood elements, including erythrocytes. However, in severe toxemia (e.g., immune complex deposition), polymorphonuclear leukocytes may degranulate directly within the vascular lumen. The release of hydrolases damages the vessel wall and enhances exudation.
Chronology and Etiology
The speed and sequence of cellular emigration depend on the duration and etiology of the inflammation.
- 6–24 hours: Neutrophils dominate the exudate.
- 24–48 hours: Monocytes and lymphocytes predominate.
Etiological factors can alter this timeline. Bacterial infections invariably recruit neutrophils first. Viral infections or tuberculosis prompt an initial vanguard of lymphocytes. Immune-mediated inflammation triggers active eosinophil migration.
Within the lesion, leukocytes serve a dual function. On one hand, they provide defense via phagocytosis and pathogen destruction. On the other hand, they cause tissue destruction: lysosomal hydrolases and toxic oxygen species damage host tissues, leading to cellular debris accumulation.