Crotoxin promotes macrophage reprogramming towards an antiangiogenic phenotype

Author(s)

Pimenta, Luciana de Araujo ^{[1, 2]} ; de Almeida, Maira Estanislau S. ^{[1, 3]} ; Bretones, Marisa Langeani ^[1] ; Cirillo, Maria Cristina ^[1] ; Curi, Rui ^{[4, 5]} ; Sampaio, Sandra Coccuzzo ^{[1, 2]}

Affiliation

^[1] Butantan Inst, Lab Pathophysiol, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Cell & Dev Biol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

^[5] Univ Cruzeiro Sul, Interdisciplinar Postgrad Program Hlth Sci, 868 Galvao Bueno, BR-01506000 Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, MAR 12 2019.
• Web of Science Citations: 0

Abstract

Crotoxin (CTX) is the primary toxin of South American rattlesnake Crotalus durissus terrificus venom. CTX reduces tumour mass, and tumour cell proliferation and these effects seem to involve the formation of new vessels. Angiogenesis has a key role in tumour growth and progression and is regulated by macrophage secretory activity. Herein, the effect of CTX on macrophage secretory activity associated with angiogenesis was investigated in vitro. Thymic endothelial cells (EC) were incubated in the presence of macrophages treated with CTX (12.5 nM) or supernatants of CTX-treated macrophages and endothelial cell proliferation, migration and adhesion activities, and the capillarylike tube formation in the matrigel-3D matrix was measured. Angiogenic mediators (MMP-2, VEGF and TNF-alpha) were measured in the cell culture medium. Macrophages pre-treated with CTX and supernatant of CTX-treated macrophages inhibited EC proliferation, adhesion to its natural ligands, and migration (as evaluated in a wound-healing model and Time Lapse assay) activities. Decreased capillary-like tube formation and MMP-2, VEGF and TNF-alpha levels in the supernatant of macrophages treated with CTX was also described. CTX promotes macrophage reprogramming towards an antiangiogenic phenotype. (AU)

• FAPESP's process: 13/17190-7 - Effect of crotoxin on the modulating action of macrophages on angiogenesis: in vitro assays
• Grantee: Luciana de Araújo Pimenta
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/51241-5 - Effect of Crotoxin on several steps in angiogenese evaluated in two dimensional and three dimensional matrices: in vitro studies
• Grantee: Sandra Coccuzzo Sampaio Vessoni
• Support Opportunities: Regular Research Grants