Research ResourceImmunology

Systems-Level Analysis of Proteolytic Events in Increased Vascular Permeability and Complement Activation in Skin Inflammation

Sci. Signal.  15 Jan 2013:
Vol. 6, Issue 258, pp. rs2
DOI: 10.1126/scisignal.2003512

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Taking a Snapshot of Inflammation

Studies of inflammatory mediators, such as proteases and their inhibitors, often involve in vitro analyses or focus on a single target in vivo. However, given the complex interplay among all of the players in the inflammatory response, a system-wide analysis would provide a better understanding of how each factor works in its natural environment. With their approach of quantitatively labeling the N termini of proteins (both uncleaved and after protease-mediated cleavage) from inflamed mouse skin tissue, auf dem Keller et al. provide a snapshot of the inflammatory response in vivo. Their analysis identified previously uncharacterized cleavage events within the complement cascade and highlighted a role for matrix metalloproteinase 2, which contributed to increased blood vessel permeability during inflammation. Together, these data provide a system-wide proteolytic fingerprint of skin inflammation and generate functional hypotheses that warrant further investigation.