Overview of the naturally occurring CXCL8 isoforms.

<p>Several NH₂-terminally modified isoforms of CXCL8 have been purified from the conditioned medium of leukocytes, fibroblasts and endothelial cells. The NH₂-terminal and COOH-terminal sequences of these isoforms are depicted in the one-letter code (B = citrulline). Based on the criteria formulated by Von Heijne <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023913#pone.0023913-vonHeijne1" target="_blank">[29]</a>, the 99 amino acid precursor molecule may be cleaved by signal peptidases between Cys₂₀ and Glu₂₁ or between Gly₂₂ and Ala₂₃, the latter being more probable. Indeed both resulting CXCL8 proteins have been identified and are indicated in this manuscript as CXCL8(-2-77) and CXCL8(1-77), respectively. CXCL8(1-77) can be cleaved by a number of proteases, resulting in the listed NH₂-terminally truncated forms. Furthermore, CXCL8 can be citrullinated by peptidylarginine deiminase (PAD). These NH₂-terminal modifications differently affect the ability of CXCL8 to recruit neutrophils. The <i>in vivo</i> neutrophil-attracting activity is defined in the boxes at the right. CXCL8(-2-77), CXCL8(1-77), CXCL8(2-77) and CXCL8(3-77) show comparable intermediate activity. The more extensively truncated isoforms CXCL8(6-77), CXCL8(7-77), CXCL(8-77) and CXCL8(9-77), in contrast, display enhanced neutrophil recruiting potency, whereas citrullination significantly lowers the capacity of CXCL8 to guide neutrophils. (MMP, matrix metalloprotease).