C5a and Neutrophils as Early Mediators in Inflammatory Arthritis Save

Researchers from the Massachusetts General Hospital (MGH) have studied the initial steps in an animal model of inflammatory arthritis and found that complement C5a is critical to neutrophils migration into joints. The findings of these early events in the inflammatory cascade were published in Science Immunology. (Citation source: http://buff.ly/2kpeR5D)

Historically it has been thought that the earliest events in the synovium lead to the release of proinflammatory cytokines that activate the endothelium to to promote the adhesion and migration of inflammatory cells.

Using multiphoton intravital microscopy was used to assess cellular events with the induction of IC-induced arthritis in a mouse model of rheumatoid arthritis. Their experiments revealed that the presence of ICs within the joint space induces the generation of complement C5a, C5a directly initiates neutrophils adhesion and transendothelial migration. 

Neutrophils within the joint space release interleukin-1 IL-1) and chemokines (CCR1, CXCR2 ) that further facilitate the movement of neutrophils into the joint space.

This method of imaging early events suggests an important role for C5a in the initiation of neutrophil adhesion on the joint endothelium thereby igniting inflammation.