| First Author | Barata L | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 6 | Pages | 2886-95 |
| PubMed ID | 23390291 | Mgi Jnum | J:193605 |
| Mgi Id | MGI:5468854 | Doi | 10.4049/jimmunol.1202536 |
| Citation | Barata L, et al. (2013) Deletion of Crry and DAF on Murine Platelets Stimulates Thrombopoiesis and Increases Factor H-Dependent Resistance of Peripheral Platelets to Complement Attack. J Immunol 190(6):2886-95 |
| abstractText | Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. CrryDAF mice were viable on a C3 background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre-Crry mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre-Crry bone marrows showed platelets from C3 but not C3 recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre-Crry mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre-Crry mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre-Crry mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies. |
