Table 2.
Non-exhaustive list of FPR ligands and their biological actions.
| Ligand | Biological Action | Disease State | Refs |
|---|---|---|---|
| FPR agonists | |||
| Aβ42 (FPR2/ALX) | Chemotaxis of mononuclear cells | Bacterial pathogenesis | [90] |
| Ac2-12 (FPR1) | Cardioprotection in experimental MI/R | MI [58] | [58] |
| Ac2-26 (FPR1, FPR2/ALX) |
Decreases neutrophil–endothelium interactions in flow chamber Regulates leukocyte–platelet response in the cerebral microvasculature Decreases pulmonary arterial pressure Decreases inflammatory cytokine production Decreases lung tissue damage following I/R Decreases infarct size post myocardial I/R Reduces myeloperoxidase activity Prevents IFN-γ and endotoxin induced inotropic and cyclooxygenase 2 gene expression Decreases adhesion and transmigration in inflammatory mesentery in vivo |
AIS [31] I/R induced lung injury [91] MI [33,58] Mesenteric ischemia [84] |
[31,33,58,84,91] |
| Ac9–25 (FPR1) | Activates neutrophil NADPH oxidase | Inflammation | [92] |
| Annexin A1 (FPR2/ALX) | Regulates microglial efferocytosis and phagocytosis Decreases neutrophil–endothelium interactions in flow chamber Cardioprotection in experimental MI/R Prevents leukocyte migration to the inflamed tissue |
AIS [93] MI [58] |
[58,93] |
| Antiflammin 2 (FPR2/ALX) | Decreases neutrophil–endothelium interactions | Inflammation | [22] |
| Cathepsin G (FPR1) | Chemoattractant for phagocytic leukocytes Promotes platelet aggregation and hemostasis Promotes thrombus formation Promotes middle cerebral artery occlusion and brain injury in ischemic stroke model |
AIS [94] | [94,95] |
| CRAMP (FPR2/ALX) | Chemotactic activator of mouse and human leukocytes Calcium flux, MAPK activation |
Bacterial pathogenesis | [96] |
| Compound 17b (FPR1, FPR2/ALX) | Attenuates early as well as late inflammatory responses after via ERK1/2–Akt kinase system | MI [64] | [64] |
| D2D388–274 (FPR2/ALX) | Inhibits monocyte chemotaxis and integrin-dependent cell adhesion | Inflammation | [97] |
| fMLP and analogues (FPR2/ALX) | Defective PMN chemotaxis in juvenile peridontitis in vivo Lineage specific differentiation of mesenchymal stem cells especially osteoblasts |
Juvenile periodontitis [98] Osteoporosis [99] |
[98,99] |
| Formylated humanin (FPR2/ALX) | Chemotaxis of human FPR2/ALX-transfected CHO cells | Inflammation | [100] |
| Humanin (FPR2/ALX) | Chemotaxis of human FPR2/ALX-transfected CHO cells | Inflammation | [100] |
| HIV-1 T20 (DP178) (FPR1, FPR2/ALX) | Chemoattractant and activator of peripheral phagocytes, hence promoting host immune responses against HIV-1 replication | HIV/AIDS [101,102] | [101,102] |
| HIV-1 T21 (DP107) (FPR1, FPR2/ALX) | Chemoattractant and activator of peripheral phagocytes (high affinity towards FPR2/ALX) | HIV/AIDS [103] | [103] |
| HIV gp41 (N36) (FPR2/ALX) | Induces directional migration and calcium mobilization in human monocytes and neutrophils | HIV/AIDS [104] | [104] |
| Lipoxin A4 and ATL (aspirin triggered lipoxin) | Inhibition of lung inflammation after hind-limb IR Downregulation of neutrophil accumulation Regulates neutrophil–platelet aggregates ATL is required for ASA protection in AIS |
Hind limb ischemia [105] AIS [31] |
[31,105] |
| LL-37 (cathelicidin peptide) (FPR2/ALX) | Enhances phagocytosis of IgG-opsonized Gram negative and Gram-positive bacteria Chemoattractant for human peripheral blood neutrophils, monocytes and T cells Calcium mobilization | Bacterial pathogenesis | [106] |
| MMK-1 (FPR2/ALX) | Potent chemoattractant and calcium mobilizing agent agonist for human monocytes, neutrophils and FPR2/ALX transfected human embryonic kidney (HEK) 293 cells. | Bacterial pathogenesis | [107] |
| N36 peptide (FPR2/ALX) | Chemotaxis and calcium mobilization in monocytes and neutrophils | Viral pathogenesis | [104] |
| NADH dehydrogenase (FPR2/ALX) | Chemotaxis and calcium mobilization in human FPR2/ALX-expressing HL-60 cells | Inflammation | [108] |
| PACAP27 (FPR2/ALX) | Neutrophil chemotaxis and upregulation of CD11b Intracellular calcium mobilization ERK phosphorylation |
Inflammation | [109] |
| PRP106-126 (FPR2/ALX) | Endocytosis in glial cells | Neurodegenerative diseases | [110] |
| Quin-C1 (FPR2/ALX) | Neutrophil chemotaxis, stimulates calcium mobilization, and MAP kinase phosphorylation | Inflammation | [111] |
| Rana-6 (FPR2/ALX) | Chemoattractant of phagocytes | Inflammation | [112] |
| SRSRY (FPR1) | Directional cell migration on vitronectin-coated filters | Inflammation | [113] |
| Serum amyloid A (SAA) (FPR2/ALX) | Potent leukocyte chemoattractant | Inflammation | [114] |
| Temporin A (FPR2/ALX) | Chemoattractant and activator of peripheral phagocytes | Bacterial pathogenesis | [96] |
| uPAR84–95 (FPR2/ALX) | Chemoattractant and activator of peripheral phagocytes (high affinity) | Inflammmation | [115] |
| V3 peptide | Chemoattractant of phagocytes Inhibits monocytic response to chemokines |
Inflammation | [115] |
| W peptide (FPR2/ALX) | Activates phagocyte chemotaxis and calcium flux | Inflammation | [116] |
| FPR antagonists | |||
| BOC2 (FPR1, FPR2/ALX) | Decreased neutrophil activation | Inflammation | [117] |
| CDCA (FPR1) | Inhibits neutrophil chemoattraction and migration Inhibits calcium flux |
Leukocyte migration/Inflammation | [118] |
| CHIPS (FPR1) | Inhibits chemotaxis in S. aureus infection | Bacterial pathogenesis | [119] |
| Coronavirus 229E peptides (FPR2/ALX) | Ligand binding studies using transfected CHO cells demonstrated antagonism of FPR2/ALX | Viral/bacterial pathogenesis | [120] |
| Coronavirus peptides (FPR2/ALX) | Inhibits fMLP interaction in CHO cells | Viral/bacterial pathogenesis | [120] |
| Cyclosporine A (FPR1) | Inhibits fMLF-stimulated degranulation, chemotaxis, calcium mobilization of neutrophils | Inflammation | [121] |
| Cyclosporine H (FPR1) | Decreased neutrophil activation | Inflammation | [117] |
| DCA (FPR1) | Inhibits fMLP-induced monocyte and neutrophil chemotaxis and calcium mobilization | Inflammation | [112] |
| Ebola peptides (FPR1) | Inhibits fMLP interaction in CHO cells | Viral pathogenesis | [120] |
| FLIPr (FPR2/ALX) | FPR2/ALX inhibitory protein (FLIPr) exerts anti-inflammatory activity by inhibiting calcium mobilization and cell migration toward chemoattractants. | Inflammation | [122] |
| HIV-2 peptides (FPR1) | Inhibits fMLP interaction in CHO cells | Viral pathogenesis | [120] |
| Isopropylureido-FLFLF (FPR1) | Inhibits chemotaxis | Inflammation | [123] |
| Spinorphin (FPR1) | Inhibits calcium mobilization and fMLP induced neutrophil chemotaxis | Inflammation | [124] |
| WRW4 (FPR2/ALX) | Inhibits chemotaxis, calcium flux, superoxide generation and ERK phosphorylation | Neurodegenerative diseases, AIS | [125] |
MI, myocardial infarction; MI/R, myocardial ischemia reperfusion; AIS, acute ischemic stroke; IFN-γ, interferon gamma; MAPK, Mitogen-activated protein kinase; ERK, extracellular signal–regulated kinase; AKT, serine/threonine-protein kinase; PMN, polymorphonuclear leukocytes; CHO cells, Chinese hamster ovary; ATL, aspirin triggered lipoxin; ASA, aspirin ; IgG, Immunoglobulin G; fMLP, formyl-Met-Leu-Phe (fMLP), G proteins; FLIPr, FPR2/ALX inhibitory protein