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Members of the Consolidated Research Group Macrophage Biology, located at PCB. Photo: UB.
 14.09.2015

Protein NBS1 is crucial for macrophage functional activity

Protein NBS1, which plays a key role in DNA damage repair, is required for macrophage functional activity. This is one of the conclusions of a scientific paper published in the journal Blood—considered one of the best scientific publications in the field of haematology— and signed by a team of experts from the Faculty of Biology of the University of Barcelona (UB), Consolidated Research Group Macrophage Biology –located at the Barcelona Science Park (PCB)– and the Institute for Research in Biomedicine (IRB Barcelona). The protein also has implications for understanding the immune defects observed in patients with Nijmegen breakage syndrome and other related disorders.

 

Protein NBS1 (Nijmegen breakage syndrome 1) is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response and cell signalling. In the study published in the journal Blood (doi: http://dx.doi.org/10.1182/blood-2015-04-637371) the scientific team has examined the role of NBSI in macrophage function. Macrophages are immune system cells able to produce great quantities of reactive oxygen species that can damage DNA. The research has been developed with a knockout (KO) mouse model genetically modified to not express the gene that codifies protein NBS1.  

According to results, when macrophages are activated by pro-inflammatory (IFN-γ and LPS) stimuli, NBS1 absence produces DNA breaks, which causes defects in proliferation, delayed differentiation and increased senescence. Moreover, these cells show an increased expression of pro-inflammatory cytokines, molecules that favour autoimmune processes and disorders in in vivo models of inflammatory diseases.

This new study provides new insights into the role that macrophages play in severe immunodeficiency in patients with Nijmegen breakage syndrome and similar diseases. The article is signed by Selma Pereira Lopes, Juan Tur, Juan Antonio Calatayud-Subias, Jorge Lloberas and Antonio Celada, experts in the Department of Physiology and Immunology (Faculty of Biology of the UB and PCB), who are members of the Consolidated Research Group Macrophage Biology, and Travis H. Stracker, researcher at the IRB Barcelona.

The Consolidated Research Group Macrophage Biology – led by Antonio Celada, professor in the Department of Physiology and Immunology of UB– is focused on studying the role that macrophages play in inflammation, one of the keys of immune response. Macrophages are produced in the bone marrow and are located in all the organs of the body, where they differentiate and become microglia (brain), Kupffer cells (liver), Langerhans cells (skin), dendritic cells, among others. Macrophages are critical in the immune system as they directly phagocytize and destroy bacteria, fungi, parasites and virus. Macrophages not only destroy micro-organisms but also play a key role in wound healing, tissue repair and vascularization and these cells have important functions outside of the immune system, such as the control of iron or lipid metabolisms.