title: Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva.
abstract: Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de JaneiroRJ, Brasil.
authors.forename: Natalia Cadaxo
authors.initials: NC
authors.lastname: Rochael
authors.forename: Luize Gonçalves
authors.initials: LG
authors.lastname: Lima
authors.forename: Sandra Maria Pereira de
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Marcello André
authors.initials: MA
authors.lastname: Barcinski
authors.forename: Elvira Maria
authors.initials: EM
authors.lastname: Saraiva
authors.forename: Robson Queiroz
authors.initials: RQ
authors.lastname: Monteiro
authors.forename: Lucia Helena
authors.initials: LH
authors.lastname: Pinto-da-Silva
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D003546:Cysteine Endopeptidases; D005165:Factor V / Q000037:antagonists & inhibitors; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D065427:Factor Xa Inhibitors; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D007891:Leishmania / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010314:Partial Thromboplastin Time; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D011576:Psychodidae / Q000378:metabolism / Q000469:parasitology*; D012463:Saliva / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009363:Neoplasm Proteins; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D014020:Tissue Extracts; C022475:prothrombinase complex; D005165:Factor V; D005170:Factor X; D013917:Thrombin; D015951:Factor Xa; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant
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