Table 1.

Impact of (heterophilic) chemokine complexes on function-proposed mechanisms.

Dimer	Function	Cellular Effect	References
Enhancing effects
CXCL4●CCL5	Prevention of CCR5 internalization, prolonged signaling	Increased monocyte arrest	[61,71,85,86]
CCL5●HNP1	Binding to CCR5	Increased recruitment and adhesion of monocyte, and macrophage recruitment	[87]
CCL5●CCL17	Promotion of CCR4•CCR5 heterodimerization	Promotes Treg homeostasis	[61]
CXCL10●CCL22	Activation of CCR4, increased ERK phosphorylation	Increased T cell migration	[64]
CCL2●CXCL12	Activation of CCR2 on macrophages, increased IL-10 production and secretion	M2 macrophage polarization, IL-10-dependant B and T cell activation	[68,69]
CXCL12●HMGB1	Ternary CXCR4 complex, biased agonism, β-arrestin 1/2-recruitment, actin polymerization, receptor internalization and degradation, increased intracellular Ca2+ mobilization and ERK phosphorylation	Increased leukocyte migration	[88,89]
CXCL12●CXCL12	Binding to and internalization of ACKR1	Binding to transfected MDCK cells and primary human Duffy-positive erythrocytes	[52]
CXCL4●Gal1	Modulation of the galectin glycan-binding affinity and specificity	Increased apoptotic activity of CD3+ and CD3+CD8+ T cells	[90]
Inhibitory effects
CCL5●CXCL12	Biased CXCR4 antagonism, signaling through PI3K, Syk and BTK affected	Inhibition of platelet aggregation	[61,67]
CXCL4L1●MIF	Prevention of CXCR4 activation	Inhibition of MIF-stimulated thrombus formation and T cell migration	[62]
CXCL8●CXCL4	No experimental data addressing the molecular mechanism	Prevents CXCL8-induced activation of hematopietic progenitors	[74,75]
CXCL4●CXCL12	Ternary CXCR4 complex, biased antagonism, increased Ca2+ release	Suppression of MDA-MB 231 breast cancer cell migration	[76,77]
CXCL1●Evasin3	Absence of binding to CXCR2	Reduction of neutrophil migration	[91]
CXCL12●Gal3	Ternary complex with CXCR4, biased antagonism, decreased β-arrestin recruitment and cAMP production	Inhibition of CD4+ T cell, monocyte and neutrophil recruitment	[92]
CCL5●Gal9	Modulation of the galectin glycan-binding affinity andspecificity	Decreased apoptotic activity of CD3+ and CD3+CD4+ T cells	[90]
CXCL12●CXCL12	Biased CXCR4 antagonism and heterotrimeric G proteins, inhibition of adenylate cyclase, increased Ca2+ release and actin polymerization	Inhibition of colonic carcinoma and murine melanoma metastasis	[38,49]
Neutral effects
CXCL1●CXCL7	Activation of CXCR2, Ca2+ release, complex interaction with GAGs	CXCR2-transfected HL60 cells response comparable to that with the CXCL7/CXCL1 mixture	[40]
CXCL8●CXCL8	Ca2+ mobilization, CXCR1/2 activation and phosphorylation, ERK phosphorylation, desensitization, β-arrestin 1-dependant CXCR2 internalization	CXCR2-induced migration of HMEC and CXCR2-transfected RBL-2H3 cells	[50]
CXCL7●CXCL7	Activation of CXCR2, Ca2+ release	CXCR2-transfected HL60 cells response comparable to that with the monomer	[39]
CXCL1●CXCL1	Binding and activation of CXCR2, Ca2+ release, ERK phosphorylation	CXCR2-HL60 cells migration comparable to that with the monomer	[51]