tailieunhanh - Báo cáo khoa học: Gelatinase B/MMP-9 and neutrophil collagenase/MMP-8 process the chemokines human GCP-2/CXCL6, ENA-78/CXCL5 and mouse GCP-2/LIX and modulate their physiological activities

On chemokine stimulation, leucocytes produce and secrete proteolytic enzymes for innate immunedefencemechanisms. Some of these proteasesmodify the biological activity of the chemokines. For instance, neutrophils secrete gelatinase B (matrix metalloproteinase-9, MMP-9) and neutrophil col-lagenase (MMP-8) after stimulation with interleukin-8/ CXCL8 (IL-8). Gelatinase B cleaves and potentiates IL-8, generating a positive feedback. | Eur. J. Biochem. 270 3739-3749 2003 FEBS 2003 doi Gelatinase B MMP-9 and neutrophil collagenase MMP-8 process the chemokines human GCP-2 CXCL6 ENA-78 CXCL5 and mouse GCP-2 LIX and modulate their physiological activities Philippe E. Van den Steen Anja Wuyts Steven J. Husson Paul Proost Jo Van Damme and Ghislain Opdenakker Laboratories of Molecular Immunology and Immunobiology Rega Institute University of Leuven Belgium On chemokine stimulation leucocytes produce and secrete proteolytic enzymes for innate immune defence mechanisms. Some of these proteases modify the biological activity of the chemokines. For instance neutrophils secrete gelatinase B matrix metalloproteinase-9 MMP-9 and neutrophil collagenase MMP-8 after stimulation with interleukin-8 CXCL8 IL-8 . Gelatinase B cleaves and potentiates IL-8 generating a positive feedback. Here we extend these findings and compare the processing of the CXC chemokines human and mouse granulocyte chemotactic protein-2 CXCL6 GCP-2 and the closely related human epithelialcell derived neutrophil activating peptide-78 CXCL5 ENA-78 with that of human IL-8. Human GCP-2 and ENA-78 are cleaved by gelatinase B at similar rates to IL-8. In addition GCP-2 is cleaved by neutrophil collagenase but at a lower rate. The cleavage of GCP-2 is exclusively N-ter-minal and does not result in any change in biological activity. In contrast ENA-78 is cleaved by gelatinase B at eight positions at various rates finally generating inactive fragments. Physiologically sequential cleavage of ENA-78 may result in early potentiation and later in inactivation of the chemokine. Remarkably in the mouse which lacks IL-8 which is replaced by GCP-2 LIX as the most potent neutrophil activating chemokine N-terminal clipping and twofold potentiation by gelatinase B was also observed. In addition to the similarities in the potentiation of IL-8 in humans and GCP-2 in mice the conversion of mouse GCP-2 LIX by mouse gelatinase B is .