Cleavage of chemokines CCL2 and CXCL10 by matrix metalloproteinases-2 and-9: implications for chemotaxis
H Denney, MR Clench, MN Woodroofe - Biochemical and biophysical …, 2009 - Elsevier
H Denney, MR Clench, MN Woodroofe
Biochemical and biophysical research communications, 2009•ElsevierProteolytic processing of chemokines is a complex process that can result in dramatic effects
on their chemotactic activity. Results from gel electrophoresis and mass spectrometry using
recombinant CCL2 and CXCL10, incubated with either MMP-2 or-9, indicate that both
chemokines are cleaved by the enzymes. N-terminal truncation of four amino acids from
CCL2, and four or five residues from CXCL10 occurred, but removal of four residues from
the C-terminus of CXCL10 was also observed with both MMPs. The speed of the reaction …
on their chemotactic activity. Results from gel electrophoresis and mass spectrometry using
recombinant CCL2 and CXCL10, incubated with either MMP-2 or-9, indicate that both
chemokines are cleaved by the enzymes. N-terminal truncation of four amino acids from
CCL2, and four or five residues from CXCL10 occurred, but removal of four residues from
the C-terminus of CXCL10 was also observed with both MMPs. The speed of the reaction …
Proteolytic processing of chemokines is a complex process that can result in dramatic effects on their chemotactic activity. Results from gel electrophoresis and mass spectrometry using recombinant CCL2 and CXCL10, incubated with either MMP-2 or -9, indicate that both chemokines are cleaved by the enzymes. N-terminal truncation of four amino acids from CCL2, and four or five residues from CXCL10 occurred, but removal of four residues from the C-terminus of CXCL10 was also observed with both MMPs. The speed of the reaction was chemokine-dependent, with N-terminal processing of CCL2 being complete within 3h, whereas activity of the MMPs on CXCL10 remained incomplete at 48h. The effect on the chemotactic potential of N-terminal truncation of CCL2 by MMPs-2 and -9 was investigated using in vitro migration assays. Monocytic cells exhibited a 2-fold reduction in migration to MMP-cleaved CCL2 variants, compared to intact CCL2.
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