Leukocyte emigration

Chemotaxis and triggering factors

The process begins with chemotaxis, the directed movement of phagocytes and mediator-producing cells to the site of injury. Various chemoattractants serve as signals. These include immunoglobulins, C-reactive protein, cytokines (IL-1, IL-8, TNF-α), complement fractions (C5a, C3a), as well as microorganisms and their toxins. Lipid mediators (leukotriene B4, thromboxane A2), bradykinin, cationic proteins, immune complexes, and fibrin and collagen degradation products play an important role.

The dynamics of mediator release are strictly ordered:

1. Immediately after tissue damage, kinins, thrombin, and proserinesterases are released. Activation of the latter triggers a cascade of molecular transformations.
2. When blood vessels are involved, fibrinogen and the complement system are activated.

As a result, basophils, eosinophils, monocytes, platelets, mast cells, and APUD system cells rush into the focus. Meanwhile, resident macrophages produce cytokines themselves, enhancing chemoattraction.

Margination and adhesion

The exit of a leukocyte from the bloodstream begins with margination (peripheral orientation). As blood flow slows down, cells leave the axial stream and shift toward the parietal layer.

Normally, the endothelium and leukocytes are negatively charged, so they mutually repel. During inflammation, plasma cations (Ca2+, Mn2+, Mg2+) recharge the endothelial surface to positive. Negatively charged leukocytes are physicochemically attracted to the vessel wall.

Next, molecular adhesion occurs. Leukocytes enter an activated state and form adhesion molecules under the action of interleukins, leukotriene B4, α-interferon, TNF-α, and bacterial lipopolysaccharides. Complement fractions (C5a, C1, C3) and IgG Fc fragments promote the attachment itself. Endotheliocytes, in turn, express integrins and intercellular adhesion molecules (ICAM-1, VCAM-1).

Diapedesis (transmigration)

Having anchored to the wall, the leukocyte begins penetration into the tissue, known as diapedesis. Leukocyte enzymes cause endothelial cells to contract, opening up interendothelial clefts.

• The neutrophil adheres closely to the endothelium.
• The cell forms a pseudopodium that squeezes into the cleft. According to electron microscopy data, the cell nucleus remains well-defined at this moment.
• The leukocyte flows into the space between the endothelium and the basement membrane.
• The basement membrane undergoes molecular changes, allowing the cell to exit into the inflammatory focus (collagen fibers are visible behind the membrane on micrographs).

This mechanism is universal for all blood formed elements, including erythrocytes. However, in severe intoxication (e.g., during immune complex deposition), polymorphonuclear leukocytes can degranulate right inside the vessel lumen. The release of hydrolases leads to wall damage and increased exudation.

Chronology and etiology

The speed and sequence of cell emigration depend on the timing and cause of inflammation.

• 6–24 hours: neutrophil leukocyte efflux dominates.
• 24–48 hours: monocyte and lymphocyte migration prevails.

The etiological factor can alter this order. In bacterial infections, neutrophils always go first. If the cause is viruses or tuberculosis, lymphocytes make up the vanguard. In immune-mediated inflammation, eosinophils actively migrate into the tissue.

In the focus, leukocytes perform a dual function. On the one hand, it is defense: phagocytosis and destruction of irritants. On the other hand, it is destruction: hydrolases and toxic oxygen compounds destroy own tissues, leading to the formation of cellular detritus.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Cell adhesion molecules: the role of ICAM-1 and VCAM-1
• Dynamics of the release of inflammatory mediators from tissues and vessels
• Vascular wall damage by hydrolases in pronounced intoxication
• Participation of resident macrophages and APUD system cells in chemotaxis
• The dual role of leukocytes: body defense and tissue destruction

Other topics in the "Inflammation" section

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