Addressing Inflammation

with MicroLactin®

7Gingerich DA, Strobel JD. Use of Client-Specific Outcome Measures to Assess Treatment Effects in Geriatric, Arthritic Dogs: Controlled Clinical Evaluation of a Nutraceutical. Veterinary Ther. 2003; 4(1): 56-66.
Immediately after an injury occurs, local mast cells, neutrophils, and resident macrophages alert the immune system to the presence of damaged cells or foreign organisms. These sentinel cells release cytokines (such as interleukin 1 and interferon α), kinins (such as bradykinin), and vasoactive amines (such as histamine) to trigger the inflammatory process. These and other inflammatory mediators are the chemical communication signals that direct the entire inflammatory process.

Acute inflammation ensues with two phases of inflammation:
1. The vascular stage of inflammation consists of vasodilation and increased vascular permeability.
2. The cellular stage of inflammation involves the migration of leukocytes, predominantly neutrophils, into the affected tissues.

Neutrophils enter inflamed tissues and eliminate foreign organisms via phagocytosis. Additionally, they release toxic substances (e.g., degradative enzymes [elastase and collagenase]), reactive oxygen species, and proinflammatory mediators. The proinflammatory mediators amplify the inflammatory process by stimulating the bone marrow to produce more neutrophils, recruiting circulating neutrophils to the site of inflammation, and helping stimulate the arachidonic acid metabolism cascade. Circulating macrophages then migrate into the tissues to eliminate damaged cells and dying neutrophils and to help heal tissues.

Neutrophil migration3

It is imperative that the body regulate the migration of the neutrophils, as this migration requires a series of sequential steps: rolling, integrin activation, firm attachment, transmigration, and chemotaxis.

Rolling:

Circulating neutrophils come in contact with the blood vessel wall via loose interactions between selectinreceptors on endothelial cells and glycoproteins on the neutrophil. The force of the blood flow breaks the bond just as another forms a little further down the endothelium. The neutrophils form, break, and form new bonds with the selectin receptors, it appears to roll along the endothelial surface.

Integrin activation:

As neutrophils roll along the endothelium, they contact the proinflammatory chemokine called IL-8, which is expressed by endothelial cells during times of inflammation. IL-8 binds to chemokine receptors on neutrophils triggering an intercellular cascade within the neutrophil. Thus the integrin receptor on the surface of the neutrophil is activated.

Firm adhesion:

The activated integrin receptors on neutrophils bind strongly to intercellular adhesion molecules (ICAM) on the endothelial surface. This interaction is stronger than the force of blood flow, and the neutrophil stops rolling and adheres to the endothelial wall.

Transmigration:

Once adhered, the neutrophil crawls to the closest endothelial cell border. The neutrophil cytoskeleton reorganizes, dramatically changing shape. A leading edge of the neutrophil inserts itself between two endothelial cells, allowing it to exit the circulation and enter the underlying connective tissue. This process is referred to as transmigration.

Chemotaxis:

Once the neutrophil enters the affected tissue, it follows a gradient of chemokines, molecules from damaged cells and microbial products to the site of inflammation.

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