Posttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH(2)-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others.status: publishe

A Ben Baruch

A Mortier

A Rot

A Walz

A Wuyts

Anneleen Mortier

AW Segal

CA Hebert

F Wartha

G von Heijne

H Nakagawa

I Clark-Lewis

Isabelle Ronsse

J Van Damme

JM Schroder

JM Schröder

Jo Van Damme

Karolien Grauwen

M Pruenster

MA Gimbrone

Nele Berghmans

P Proost

Paul Proost

PE Van den Steen

R Snyderman

Silvano Sozzani

Steve Stegen

T Loos

T Yoshimura

V Papayannopoulos

Y Le

English

PubMed

-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others. chemotaxis of peripheral blood-derived human neutrophils. Moreover, CXCL8(-2-77) was less efficiently processed by plasmin into the more potent CXCL8(6-77). The truncated forms CXCL8(2-77) and CXCL8(3-77) had higher affinity for heparin than CXCL8(1-77), a property important for the presentation of CXCL8 on endothelial layers. Upon intraperitoneal injection in mice, elongated, truncated and intact CXCL8 were equally potent to recruit neutrophils to the peritoneal cavity.-terminal region into citrulline by peptidylarginine deiminases and has weak potency to induce neutrophil extravasation

Mortier Anneleen

Berghmans Nele

Ronsse Isabelle

Grauwen Karolien

Stegen Steve

Van Damme Jo

Proost Paul

Public Library of Science (PLOS)

Biological Activity of CXCL8 Forms Generated by Alternative Cleavage of the Signal Peptide or by Aminopeptidase-Mediated Truncation

BACKGROUND:Posttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH(2)-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others. METHODOLOGY/PRINCIPAL FINDINGS:Aminopeptidase-cleaved CXCL8(2-77) and CXCL8(3-77), the product of alternative cleavage of the signal peptide CXCL8(-2-77) and the previously studied forms containing 77 and 72 amino acids, CXCL8(1-77) and CXCL8(6-77), were prepared by solid-phase peptide synthesis, purified and folded into active proteins. No differences in binding and calcium signaling potency were detected between CXCL8(1-77), CXCL8(-2-77), CXCL8(2-77) and CXCL8(3-77) on cells transfected with one of the human CXCL8 receptors, i.e. CXCR1 and CXCR2. However, CXCL8(-2-77) was more potent compared to CXCL8(1-77), CXCL8(2-77) and CXCL8(3-77) in signaling and in vitro chemotaxis of peripheral blood-derived human neutrophils. Moreover, CXCL8(-2-77) was less efficiently processed by plasmin into the more potent CXCL8(6-77). The truncated forms CXCL8(2-77) and CXCL8(3-77) had higher affinity for heparin than CXCL8(1-77), a property important for the presentation of CXCL8 on endothelial layers. Upon intraperitoneal injection in mice, elongated, truncated and intact CXCL8 were equally potent to recruit neutrophils to the peritoneal cavity. CONCLUSIONS:In terms of their ability to induce neutrophil recruitment in vivo, the multiple CXCL8 forms may be divided in three groups. The first group includes CXCL8 proteins consisting of 75 to 79 amino acids, cleaved by aminopeptidases, with intermediate activity on neutrophils. The second group, generated through proteolytic cleavage (e.g. by Ser proteases), contains 69 to 72 amino acid forms which are highly potent neutrophil attractants in vivo. A third category is generated through the modification of the arginine in the NH(2)-terminal region into citrulline by peptidylarginine deiminases and has weak potency to induce neutrophil extravasation

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Biological activity of CXCL8 forms generated by alternative cleavage of the signal peptide or by aminopeptidase-mediated truncation.

Crossref

Mortier, Anneleen

Berghmans, Nele

Ronsse, Isabelle

Grauwen, Karolien

Stegen, Steve

Van Damme, Jo

Proost, Paul

Lirias

Biological activity of CXCL8 forms generated by alternative cleavage of the signal peptide or by aminopeptidase-mediated truncation

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Zychlinsky A

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3164136

Biological Activity of CXCL8 Forms Generated by Alternative Cleavage of the Signal Peptide or by Aminopeptidase-Mediated Truncation

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