Involvement of formyl peptide receptors in the stimulatory effect of crotoxin on macrophages co-cultivated with tumour cells

Author(s)

Costa, E. S. ^[1] ; Faiad, O. J. ^[1] ; Landgraf, R. G. ^[2] ; Ferreira, A. K. ^[3] ; Brigatte, P. ^[4] ; Curi, R. ^[5] ; Cury, Y. ^[6] ; Sampaio, S. C. ^[1]

Affiliation

^[1] Butantan Inst, Lab Pathophysiol, BR-05503900 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Lab Inflammat & Vasc Pharmacol, BR-09913030 Diadema, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, BR-01246000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

^[6] Butantan Inst, Special Lab Pain & Signaling, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Toxicon; v. 74, p. 167-178, NOV 2013.
• Web of Science Citations: 8

Abstract

Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. The present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. The effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 mu g/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. The co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. The production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. The level of secreted IL-1 beta increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA(4) (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA(4) was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• 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