Table 1.
Summary of PS receptors and soluble PS binding proteins and their relationship to autoimmunity in mouse and human systems.
| Molecule | Function | Mouse | Human |
|---|---|---|---|
| PS BRIDGING MOLECULES | |||
| GAS-6 | Bridging molecule between PS and TAM receptor | Deficiency causes platelet dysfunction and protects against thrombosis (21) | Polymorphism positively associated with cutaneous vasculitis in SLE patients (22) |
| Protein S | Bridging molecule between PS and TAM receptors | Knockout is embryonic lethal (23) | SLE patients have reduced level of circulating protein S (24, 25) |
| MGF-E8 | Bridging molecule between PS and αvβ3/β5 integrins | Deficient mice develops auto-immune disease (26) | Polymorphisms and aberrant splicing reported in some SLE patients (27, 28) |
| C1q | Acts as PS bridging molecule to SCARF1 and CD91/LRP1. C1q also binds annexin A2, A5, and CRT | Deficiency leads to auto-immune diseases (29) | Ninety percent of C1q-deficient individuals develop SLE (30) |
| MBL | Bridging molecule between PS and CD91/LRP1 | Deficiency leads to defective clearance of apoptotic cells but no auto-immune phenotype (31) | Polymorphisms are SLE risk factors (32, 33) |
| High molecular weight kininogen | Bridging molecule between PS and uPAR | NR | NR |
| Thrombospondin | Bridging molecule between PS and CD36 | NR | NR |
| CRT | Binds to PS in a complex with C1q | Knockout is embryonic lethal (34) | NR |
| PS RECEPTORS | |||
| TAM receptors | Indirectly recognize PS via protein S or GAS-6 | Tyro-3KO/AxlKO/MerKO triple knockout mice develop auto-immune diseases (35). MerKO single knockout mice develop progressive SLE-like autoimmunity (36) | Polymorphisms in Mer gene associated with multiple sclerosis susceptibility (37). Increased sMertk in advanced atheromata (38) and SLE (39) |
| Tim-4 | Directly recognize PS | Administration of anti-Tim4 mAb into mice caused auto-antibodies production (40) | NR |
| CD300f | Directly recognize PS | Deficient mice develop a SLE-like disease (41) | NR |
| SCARF1 | Indirectly recognize PS via binding to C1q | Deficient mice developed SLE-like disease (42) | NR |
| Stabilin-1/2 | Directly recognize PS | Deficient mice do not show any SLE-related phenotype (43) | NR |
| BAI-1 | Directly recognize PS | NR | NR |
| RAGE | Directly recognize PS | Deficiency causes impaired phagocytosis but no SLE-related phenotype (44) | Polymorphism associated with SLE and disease severity in lupus nephritis (45) |
| CD91/LRP1 | Indirectly recognize PS via binding to C1q and/or collectins (MBL, SP-A, SP-D) | Deficient mice are embryonic lethal (46) | SLE patients have significantly increased levels of circulating soluble CD91/LRP1 (47) |
NR, not reported.