title: Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators.
abstract: Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin.
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil 1500, Sao Paulo-SP, Brazil.
authors.forename: Vanessa O
authors.initials: VO
authors.lastname: Zambelli
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Sampaio
authors.forename: Lia S
authors.initials: LS
authors.lastname: Sudo-Hayashi
authors.forename: Karin
authors.initials: K
authors.lastname: Greco
authors.forename: Luiz R G
authors.initials: LR
authors.lastname: Britto
authors.forename: Adilson S
authors.initials: AS
authors.lastname: Alves
authors.forename: Bianca C
authors.initials: BC
authors.lastname: Zychar
authors.forename: Luis R C
authors.initials: LR
authors.lastname: Gonçalves
authors.forename: Diva D
authors.initials: DD
authors.lastname: Spadacci-Morena
authors.forename: Rosemari
authors.initials: R
authors.lastname: Otton
authors.forename: Maisa S
authors.initials: MS
authors.lastname: Della-Casa
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Yara
authors.initials: Y
authors.lastname: Cury
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D003439:Crotoxin / Q000737:chemistry / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D008084:Lipoxygenase / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008196:Lymph / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D042601:Lymphatic Vessels / Q000166:cytology / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000097:blood / Q000187:drug effects*; D008297:Male; D054467:Phospholipases A2 / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013897:Thoracic Duct / Q000166:cytology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D003439:Crotoxin; D008084:Lipoxygenase; D054467:Phospholipases A2; C063449:zileuton; D006918:Hydroxyurea