An investigation into the pro-inflammatory properties of heme in primary human macrophages

• Grant number: 14/23170-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2015
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Nicola Amanda Conran Zorzetto
• Grantee: Angélica Aparecida Antoniellis Silveira
• Supervisor: Aisling Dunne
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Trinity College Dublin, Ireland
• Associated to the scholarship: 12/22048-2 - Investigation into the pro-inflammatory properties of TNF-alpha and heme in leukocytes in vitro and in vivo., BP.DR

Abstract

Evidence suggests that haem may represent a novel DAMP. Haem generated by intra and extra-vascular haemolysis activates innate immune cells and non-hematopoietic cells, promoting pro-inflammatory activities, such as leukocyte activation, migration and infiltration, adhesion molecule activation, cytokine release and inflammasome formation. Our data suggest that haem is a potent driver of inflammatory mediator, matrix metalloprotease (MMP) and S100 protein expression in the primary human macrophages (hMACs). Here we also demonstrate that exposure of hMACs to haem induces IL-1² processing in LPS-primed hMACs in a capase-1 and NLRP3-dependent manner. We found that haem activates PI3 kinase, MEK and ERK and induces hMACs to upregulate their expressions of MMP1 and MMP9 and the damage-associated molecules, S100A8 and S100A12. We postulate that S100A8 may act as a sterile priming stimuli in intravascular hemolytic diseases and data provide new insights regarding the mechanisms by which haemoglobin and its products induce inflammatory responses. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVEIRA, ANGELICA A. A.; MAHON, OLWYN R.; CUNNINGHAM, CLARE C.; CORR, EMMA M.; MENDONCA, RAFAELA; SAAD, SARA T. O.; COSTA, FERNANDO F.; DUNNE, AISLING; CONRAN, NICOLA. S100A8 acts as an autocrine priming signal for heme-induced human M phi pro-inflammatory responses in hemolytic inflammation. Journal of Leukocyte Biology, v. 106, n. 1, p. 35-43, JUL 2019. (12/22048-2, 14/19173-5, 14/23170-1)