Hematopoietic chemokines and cytokines that bind HS
| Cytokine/chemokine . | Major roles in hematopoiesis . | HS modifications facilitating binding . | Reference . |
|---|---|---|---|
| IL-1 | Myeloid differentiation of stem and progenitor cells Response to infections Inflammation/immune response | N-sulfation (important, not required) | 9 |
| IL-2 | T-cell differentiation NK-cell activation | N-sulfation | 9 |
| IL-3 | HSPC maintenance | 6-O-sulfation | 7,10 |
| IL-4 | Mature B- and T-cell development B-cell class switching Macrophage regulator | IdoA, N-sulfation, O-sulfation | 11,12 |
| IL-5 | B-cell growth Eosinophil growth and activation | Heparin, N-sulfation | 13 |
| IL-6 | Neutrophil production Fever and acute phase response B-cell growth and development T-cell antagonist | Heparin, N-sulfation (important, not required), 2-O-sulfation | 9,14 |
| IL-7 | Stimulates lymphoid differentiation Mature B- and T-cell development Immune modulator (pro and antiinflammatory effects) | Heparin, HS (unspecified) | 15 |
| IL-8 | Granulocyte chemotaxis and phagocytosis | Broad sulfation (N-sulfation, 2-O-sulfation, 6-O-sulfation) | 16-18 |
| IL-10 | B-cell survival and growth Anti-inflammatory response Immune regulation | Heparin, N-sulfation, 2-O-sulfation (less), 6-O-sulfation (less) | 19,20 |
| IL-12 | T-cell growth, function, and differentiation | Heparin | 21 |
| IL-18 | Proinflammatory Mature T-cell differentiation | Unknown | 22 |
| IL-21 | B-cell and T-cell differentiation and maturation | N-sulfation, 2-O-sulfation (less), 6-O-sulfation (less) | 23 |
| MCP-1 (CCL2) | Leukocyte activation and recruitment | High sulfation (N-, 2-O-, 3-O-, 6-O-), 3-O-sulfation (preferred) | 18,24-27 |
| MIP 1α (CCL3) | Leukocyte activation and recruitment | 6-O-sulfation | 10 |
| MIP 1β (CCL4) | Leukocyte activation and recruitment | Unknown | 28 |
| RANTES/CCL5 | Leukocyte migration/trafficking Mediator of viral infections and immune response (eg, HIV) | Heparin, HS, 6-O-sulfation (more), 2-O-sulfation (less) | 18,29 |
| MCP-3 (CCL7) | Macrophage attractant | High sulfation | 18,26,30 |
| MCP-2 (CCL8) | Leukocyte activation and recruitment | Unknown | 26,31 |
| Eotaxin-1 (CCL11) | Granulocyte differentiation Eosinophil migration | Unknown | 32,33 |
| MCP-4 (CCL13) | Leukocyte chemotaxis | High sulfation | 18,33 |
| Eotaxin-3 (CCL26) | Eosinophil migration | Unknown | 34 |
| Stem cell factor | HSC maintenance, self-renewal, adhesion | Heparin, N-sulfation, 2-O-sulfation, 6-O-sulfation | 35 |
| Granulocyte/macrophage colony-stimulating factor | Myeloid differentiation (granulocyte and monocyte) Neutrophil migration | Unknown | 7,36 |
| Hepatocyte growth factor | HSC maintenance and mobilization | 6-O-sulfation | 37 |
| Platelet factor 4 (CXCL4) | Coagulation HSC maintenance Chemotaxis | N-sulfation, 2-O-sulfation,6-O-sulfation, (3-O-sulfation decreases binding) | 10,27,38 |
| Stromal derived factor-1 (CXCL12) | HSC survival, self-renewal, homing, and engraftment T-cell migration B-cell survival and migration | N-sulfation, 2-O-sulfation, 6-O-sulfation | 39 |
| CXCL13 | B-cell and T-cell organization in lymph nodes | Unknown | 40 |
| FGF-1 | HSC maintenance Lineage commitment Erythropoiesis | 2-O-sulfation, 6-O-sulfation (required) | 41 |
| Basic FGF (FGF2) | HSPC proliferation | N-sulfation, 2-O-sulfation, 6-O-sulfation (not required) | 18,42 |
| Vascular endothelial growth factor (only certain isoforms) | HSPC survival Erythropoiesis | 6-O-sulfation (more), N-sulfation (less), 2-O-sulfation (less) | 43,44 |
| Heparin binding–epidermal growth factor-like growth factor | Myeloid and lymphoid differentiation | 6-O-sulfation | 45 |
| Platelet–derived growth factor | Megakaryocyte and platelet proliferation and development | N-sulfation, 6-O-sulfation | 46 |
| APRIL | B-cell growth and survival Plasma cell function | C5-epimerization | 47,48 |
| IFN-γ–inducible protein 10 (CXCL10) | Leukocyte chemoattractant T-cell proliferation and trafficking | HS, 6-O-sulfation (more), 2-O-sulfation (less) | 18,49 |
| IFN-γ | HSC maintenance Immune response mediator Induces myelopoiesis Suppression of erythropoiesis and B-cell lymphopoiesis | N-sulfation | 50,51 |
| Transforming growth factor-β (only certain isoforms) | HSC quiescence Myeloid vs lymphoid commitment | Unknown | 52,53 |
| BMP-2 | HSC maintenance | N-sulfation | 54 |
| BMP-4 | HSC maintenance Differentiation Thymopoiesis | N-sulfation | 54 |
| BMP-6 | HSPC migration B-cell suppression | Unknown | 55 |
| BMP-7 | HSC maintenance | Unknown | 56 |
| Noggin | Inhibition of BMP | N-sulfation, 2-O-sulfation, 6-O-sulfation (required) | 57,58 |
| von Willebrand factor | Hemostasis and platelet adhesion | Unknown | 59 |
| Cytokine/chemokine . | Major roles in hematopoiesis . | HS modifications facilitating binding . | Reference . |
|---|---|---|---|
| IL-1 | Myeloid differentiation of stem and progenitor cells Response to infections Inflammation/immune response | N-sulfation (important, not required) | 9 |
| IL-2 | T-cell differentiation NK-cell activation | N-sulfation | 9 |
| IL-3 | HSPC maintenance | 6-O-sulfation | 7,10 |
| IL-4 | Mature B- and T-cell development B-cell class switching Macrophage regulator | IdoA, N-sulfation, O-sulfation | 11,12 |
| IL-5 | B-cell growth Eosinophil growth and activation | Heparin, N-sulfation | 13 |
| IL-6 | Neutrophil production Fever and acute phase response B-cell growth and development T-cell antagonist | Heparin, N-sulfation (important, not required), 2-O-sulfation | 9,14 |
| IL-7 | Stimulates lymphoid differentiation Mature B- and T-cell development Immune modulator (pro and antiinflammatory effects) | Heparin, HS (unspecified) | 15 |
| IL-8 | Granulocyte chemotaxis and phagocytosis | Broad sulfation (N-sulfation, 2-O-sulfation, 6-O-sulfation) | 16-18 |
| IL-10 | B-cell survival and growth Anti-inflammatory response Immune regulation | Heparin, N-sulfation, 2-O-sulfation (less), 6-O-sulfation (less) | 19,20 |
| IL-12 | T-cell growth, function, and differentiation | Heparin | 21 |
| IL-18 | Proinflammatory Mature T-cell differentiation | Unknown | 22 |
| IL-21 | B-cell and T-cell differentiation and maturation | N-sulfation, 2-O-sulfation (less), 6-O-sulfation (less) | 23 |
| MCP-1 (CCL2) | Leukocyte activation and recruitment | High sulfation (N-, 2-O-, 3-O-, 6-O-), 3-O-sulfation (preferred) | 18,24-27 |
| MIP 1α (CCL3) | Leukocyte activation and recruitment | 6-O-sulfation | 10 |
| MIP 1β (CCL4) | Leukocyte activation and recruitment | Unknown | 28 |
| RANTES/CCL5 | Leukocyte migration/trafficking Mediator of viral infections and immune response (eg, HIV) | Heparin, HS, 6-O-sulfation (more), 2-O-sulfation (less) | 18,29 |
| MCP-3 (CCL7) | Macrophage attractant | High sulfation | 18,26,30 |
| MCP-2 (CCL8) | Leukocyte activation and recruitment | Unknown | 26,31 |
| Eotaxin-1 (CCL11) | Granulocyte differentiation Eosinophil migration | Unknown | 32,33 |
| MCP-4 (CCL13) | Leukocyte chemotaxis | High sulfation | 18,33 |
| Eotaxin-3 (CCL26) | Eosinophil migration | Unknown | 34 |
| Stem cell factor | HSC maintenance, self-renewal, adhesion | Heparin, N-sulfation, 2-O-sulfation, 6-O-sulfation | 35 |
| Granulocyte/macrophage colony-stimulating factor | Myeloid differentiation (granulocyte and monocyte) Neutrophil migration | Unknown | 7,36 |
| Hepatocyte growth factor | HSC maintenance and mobilization | 6-O-sulfation | 37 |
| Platelet factor 4 (CXCL4) | Coagulation HSC maintenance Chemotaxis | N-sulfation, 2-O-sulfation,6-O-sulfation, (3-O-sulfation decreases binding) | 10,27,38 |
| Stromal derived factor-1 (CXCL12) | HSC survival, self-renewal, homing, and engraftment T-cell migration B-cell survival and migration | N-sulfation, 2-O-sulfation, 6-O-sulfation | 39 |
| CXCL13 | B-cell and T-cell organization in lymph nodes | Unknown | 40 |
| FGF-1 | HSC maintenance Lineage commitment Erythropoiesis | 2-O-sulfation, 6-O-sulfation (required) | 41 |
| Basic FGF (FGF2) | HSPC proliferation | N-sulfation, 2-O-sulfation, 6-O-sulfation (not required) | 18,42 |
| Vascular endothelial growth factor (only certain isoforms) | HSPC survival Erythropoiesis | 6-O-sulfation (more), N-sulfation (less), 2-O-sulfation (less) | 43,44 |
| Heparin binding–epidermal growth factor-like growth factor | Myeloid and lymphoid differentiation | 6-O-sulfation | 45 |
| Platelet–derived growth factor | Megakaryocyte and platelet proliferation and development | N-sulfation, 6-O-sulfation | 46 |
| APRIL | B-cell growth and survival Plasma cell function | C5-epimerization | 47,48 |
| IFN-γ–inducible protein 10 (CXCL10) | Leukocyte chemoattractant T-cell proliferation and trafficking | HS, 6-O-sulfation (more), 2-O-sulfation (less) | 18,49 |
| IFN-γ | HSC maintenance Immune response mediator Induces myelopoiesis Suppression of erythropoiesis and B-cell lymphopoiesis | N-sulfation | 50,51 |
| Transforming growth factor-β (only certain isoforms) | HSC quiescence Myeloid vs lymphoid commitment | Unknown | 52,53 |
| BMP-2 | HSC maintenance | N-sulfation | 54 |
| BMP-4 | HSC maintenance Differentiation Thymopoiesis | N-sulfation | 54 |
| BMP-6 | HSPC migration B-cell suppression | Unknown | 55 |
| BMP-7 | HSC maintenance | Unknown | 56 |
| Noggin | Inhibition of BMP | N-sulfation, 2-O-sulfation, 6-O-sulfation (required) | 57,58 |
| von Willebrand factor | Hemostasis and platelet adhesion | Unknown | 59 |
The table summarizes hematopoietic cytokines shown to bind HS, their general roles in hematopoietic cell function, and what is currently known about HS characteristics that are required for or facilitate/impede binding.
APRIL, a proliferation-inducing ligand; BMP, bone morphogenic protein; IFN-γ, interferon gamma; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; RANTES/CCL5, regulated upon activation, normal T-cell expressed and presumably secreted.