title: Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O).
abstract: Elevated numbers of activated platelets circulate in patients with chronic inflammatory diseases, including atherosclerosis and coronary disease. Activated platelets can activate the complement system. Although complement activation is essential for immune responses and removal of spent cells from circulation, it also contributes to inflammation and thrombosis, especially in patients with defective complement regulation. Proinflammatory activated leukocytes, which interact directly with platelets in response to vascular injury, are among the main sources of properdin, a positive regulator of the alternative pathway. The role of properdin in complement activation on stimulated platelets is unknown. Our data show that physiological forms of human properdin bind directly to human platelets after activation by strong agonists in the absence of C3, and bind nonproportionally to surface CD62P expression. Activation of the alternative pathway on activated platelets occurs when properdin is on the surface and recruits C3b or C3(H2O) to form C3b,Bb or a novel cell-bound C3 convertase [C3(H2O),Bb], which normally is present only in the fluid phase. Alternatively, properdin can be recruited by C3(H2O) on the platelet surface, promoting complement activation. Inhibition of factor H-mediated cell surface complement regulation significantly increases complement deposition on activated platelets with surface properdin. Finally, properdin released by activated neutrophils binds to activated platelets. Altogether, these data suggest novel molecular mechanisms for alternative pathway activation on stimulated platelets that may contribute to localization of inflammation at sites of vascular injury and thrombosis.
authors.affiliation: Department of Medical Microbiology and Immunology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA.
authors.forename: Gurpanna
authors.initials: G
authors.lastname: Saggu
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortes
authors.forename: Heather N
authors.initials: HN
authors.lastname: Emch
authors.forename: Galia
authors.initials: G
authors.lastname: Ramirez
authors.forename: Randall G
authors.initials: RG
authors.lastname: Worth
authors.forename: Viviana P
authors.initials: VP
authors.lastname: Ferreira
mesh_terms: D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology* / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000502:physiology*; D006801:Humans; D015539:Platelet Activation / Q000502:physiology*; D011414:Properdin / Q000276:immunology* / Q000378:metabolism
chemical_list: D003176:Complement C3; D011414:Properdin