Deletion of crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack

Barata, Lidia, Miwa, Takashi, Sato, Sayaka, Kim, David, Mohammed, Imran ORCID: https://orcid.org/0000-0002-8412-0768 and Song, Wen Chao 2013. Deletion of crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack. The Journal of Immunology 190 (6) , pp. 2886-2895. 10.4049/jimmunol.1202536

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Abstract

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. Crry−/−DAF−/− 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+-Crryflox/flox mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre+-Crryflox/flox bone marrows showed platelets from C3−/− but not C3+/+ recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre+-Crryflox/flox mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre+-Crryflox/flox mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre+-Crryflox/flox 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
ISSN:	0022-1767
Date of Acceptance:	8 January 2013
Last Modified:	11 Nov 2022 09:02
URI:	https://orca.cardiff.ac.uk/id/eprint/152686

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