Protease / Chemokine / Effectsa / Cleavage site / Refs
CD26 (DPPIV)b / CXCL6 / + / GP¯VSAVLTELRCTC / [1]
CXCL9 / +/- / TP¯VVRKGRCSC / [2,3]
CXCL10 / +/- / VP¯LSRTVRCTC / [2,3]
CXCL11 / +/- / FP¯MFKRGRCLC / [2,3]
CXCL12 / - / KP¯VSLSYRCPC / [3–8]
CCL3L1 / +++ / AP¯LAADTPT / [3,9,10]
CCL5 / 0 (CCR1, CCR3)c / SP¯YSSDTTPCC / [1,3,11,12]
CCL5 / +++ (CCR5) / SP¯YSSDTTPCC / [1,11,12]
CCL11 / +/-d / GP¯ASVPTTCC / [3,13]
CCL22 / 0 / GP¯YG¯ANMEDSVCC / [3,14,15]
MMP-1 / CXCL12 / 0 / KPVS¯LSYRCPC / [16]
CCL2 / - / QPDA¯IISPVTCC / [17]
CCL7 / --- / QPVG¯INTSTTCC / [17]
CCL13 / --- / QPD¯A¯LNV¯PSTCC / [17]
MMP-2 / CXCL12 / 0 / KPVS¯LSYRCPC / [16]
CCL7 / --- / QPVG¯INTSTTCC / [17,18]
MMP-3 / CXCL12 / 0 / KPVS¯LSYRCPC / [16]
CCL2 / - / QPDA¯IISPVTCC / [17]
CCL7 / --- / QPVG¯INTSTTCC / [17]
CCL8 / --- / QPDS¯VSIPITCC / [17]
CCL13 / --- / QPD¯A¯LNVPSTCC / [17]
MMP-8 / CCL2 / - / QPDA¯IISPVTCC / [17]
MMP-9 / CTAP-IIIe / 0 / Multiple Sites / [19]
CXCL1 / 0 / Multiple Sites / [19]
CXCL4 / 0 / Multiple Sites / [19]
CXCL8 / +++ / AVLPRS¯AKELRCQC / [19]
CXCL12 / 0 / KPVS¯LSYRCPC / [16]
MMP-13 / CXCL12 / 0 / KPVS¯LSYRCPC / [16]
CCL7 / --- / QPVG¯INTSTTCC / [17]
MMP-14 / CXCL12 / 0 / KPVS¯LSYRCPC / [16]
CCL7 / --- / QPVG¯INTSTTCC / [17]
Cathepsin G / CXCL5 / +++ / AGPAAAVL¯RELRCVC / [20]
CXCL12 / 0 / KPVSL¯SYRCPC / [21,22]
Cathepsin D / CCL3 / 0 / Multiple Sites / [23]
CCL4 / 0 / Multiple Sites / [23]
CCL21 / 0 / …KEL¯WVQQf / [23]
Cathepsin L / CXCL8 / +++ / AVLPR¯SAKELR / [24]
Elastase / CXCL12 / 0 / KPV¯SLSYRCPC / [22,25,26]
uPA / CCL14 / +++ / TKTESSSR¯GPYHPSECC / [27,28]
a, Truncated chemokines have increased (+++), unchanged (+) or reduced (+/-) activity, strong (---) or weak (-) antagonistic activity or no activity (0).
bAbbreviations: DPPIV, dipeptidyl peptidaseIV; MMP, matrix metalloproteinase; NAP-2, neutrophil-activating peptide-2; uPA, urokinase plasminogen activator.
cCD26 (DPPIV) cleaved CCL5 is inactive on CCR1 and CCR3, but has increased activity on CCR5.
dCD26 (DPPIV) cleaved CCL11 has reduced chemotactic activity but retains full HIV-suppressor activity.
eConnective tissue-activating peptideIII (CTAP-III) is the NH2-terminally extended, inactive precursor of CXCL7 (NAP-2).
fCleavage site is between L58 and W59.
References
1 Proost, P. et al. (1998) Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J. Biol. Chem. 273, 7222–7227
2 Proost, P. et al. (2001) Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties. Blood 98, 3554–3561
3 Lambeir, A.M. et al. (2001) Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J. Biol. Chem. 276, 29839–29845
4 Proost, P. et al. (1998) Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1a. FEBS Lett. 432, 73–76
5 Christopherson, K.W. et al. (2003) Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells. Blood 101, 4680–4686
6 Ohtsuki, T. et al. (1998) Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1a by CD26/dipeptidyl peptidase IV. FEBS Lett. 431, 236–240
7 Christopherson, K.W. et al. (2002) Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 a-mediated chemotaxis of human cord blood CD34+ progenitor cells. J. Immunol. 169, 7000–7008
8 Shioda, T. et al. (1998) Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1a (SDF-1a) and SDF-1b are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage. Proc. Natl. Acad. Sci. U. S. A. 95, 6331–6336
9 Proost, P. et al. (2000) Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78b into a most efficient monocyte attractant and CCR1 agonist. Blood 96, 1674–1680
10 Struyf, S. et al. (2001) Diverging binding capacities of natural LD78b isoforms of macrophage inflammatory protein-1a to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils. Eur. J. Immunol. 31, 2170–2178
11 Oravecz, T. et al. (1997) Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. J. Exp. Med. 186, 1865–1872
12 Iwata, S. et al. (1999) CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response. Int. Immunol. 11, 417–426
13 Struyf, S. et al. (1999) CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3. J. Immunol. 162, 4903–4909
14 Proost, P. et al. (1999) Truncation of macrophage-derived chemokine by CD26/ dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction. J. Biol. Chem. 274, 3988–3993
15 Mantovani, A. et al. (2000) Macrophage-derived chemokine (MDC). J. Leukoc. Biol. 68, 400–404
16 McQuibban, G.A. et al. (2001) Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J. Biol. Chem. 276, 43503–43508
17 McQuibban, G.A. et al. (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti- inflammatory properties invivo. Blood 100, 1160–1167
18 McQuibban, G.A. et al. (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289, 1202–1206
19 Van den Steen, P.E. et al. (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-a and leaves RANTES and MCP-2 intact. Blood 96, 2673–2681
20 Nufer, O. et al. (1999) Amino-terminal processing of chemokine ENA-78 regulates biological activity. Biochemistry 38, 636–642
21 Delgado, M.B. et al. (2001) Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur. J. Immunol. 31, 699–707
22 Levesque, J.P. et al. (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J. Clin. Invest. 111, 187–196
23 Wolf, M. et al. (2003) Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1a, macrophage inflammatory protein-1b, and SLC that are expressed in human breast cancer. Am. J. Pathol. 162, 1183–1190
24 Ohashi, K. et al. (2003) Identification of interleukin-8 converting enzyme as cathepsin L. Biochim. Biophys. Acta 1649, 30–39
25 Valenzuela-Fernandez, A. et al. (2002) Leukocyte elastase negatively regulates Stromal cell-derived factor-1 (SDF-1)/CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4. J. Biol. Chem. 277, 15677–15689
26 Petit, I. et al. (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat. Immunol. 3, 687–694
27 Vakili, J. et al. (2001) Urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active. J. Immunol. 167, 3406–3413
28 Detheux, M. et al. (2000) Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties. J. Exp. Med. 192, 1501–1508