A Technique to Generate an Adjuvant-Induced Arthritis Mouse Model
Transkript
To generate an adjuvant-induced arthritis mouse model, begin with an anesthetized mouse in the prone position.
Take a syringe containing complete Freund's adjuvant or CFA, a suspension of heat-killed Mycobacterium tuberculosis in oil. Inject the CFA into the ankle joint space — a synovial fluid-filled region between the lower leg bone and foot bone — followed by injection into the tissue surrounding the joint, inducing chronic inflammation.
The fluid-filled cavity is bordered by a synovial membrane, consisting of a lining layer enriched with macrophages and fibroblasts — functioning as an immunological barrier — and a sub-lining interstitial tissue.
The macrophages recognize the bacterial antigen and transform to a phagocytic phenotype, disrupting the barrier integrity. The macrophages also release chemoattractants and cytokines. The released chemoattractants mediate the recruitment of circulatory neutrophils to the infection site.
Recognition of the bacterial antigen activates neutrophils, resulting in degranulation. Released matrix metalloproteinases and proteases cause cartilage damage and sustained inflammation.
Macrophage-secreted cytokines also bind to receptors on the synovial fibroblasts. The cytokine binding and antigen recognition induce fibroblast activation.
Activated fibroblasts undergo abnormal proliferation, resulting in synovial hyperplasia — leading to excess synovial fluid production and joint swelling, characteristic of arthritis.
