Anti-Msr1 monoclonal antibody, clone 2F8 [FITC]

Introduction: We investigated whether or not inherited variation in MSR1, RNASEL and E-cadherin contribute to prostate cancer risk in Poland. Material and Methods: We sequenced the coding region of these three genes in individuals from Poland and identified five common DNA variants (R462Q and D541E in RNASEL, R293X and P275A in MSR1, and 2076C > T (A692A) in E-cadherin). These five variants and the -160C > A promoter change in E-cadherin were genotyped in 737 prostate cancer cases and 511 controls. Results: The frequencies of genotyped variants in MSR1, RNASEL and E-cadherin genes in cases and controls were similar. We did not see any association for the studied variants when cases were stratified by age of diagnosis, by family history, by prostate-specific antigen level at the time of diagnosis, by Gleason sore or by tumor stage. Conclusions: Inherited variation in RNASEL, MSR1 and E-cadherin genes do not seem to contribute to prostate cancer development in Poland.

Background Microglia, the primary resident myeloid cells of the brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfunction has been implicated in a number of central nervous system (CNS) disorders, thus developing tools to manipulate and replace these myeloid cells in the CNS is of therapeutic interest. Methods Using whole body irradiation, bone marrow transplant, and colony-stimulating factor 1 receptor inhibition, we achieve long-term and brain-wide (similar to 80%) engraftment and colonization of peripheral bone marrow-derived myeloid cells (i.e., monocytes) in the brain parenchyma and evaluated the long-term effects of their colonization in the CNS. Results: Here, we identify a monocyte signature that includes an upregulation in Ccr1, Ms4a6b, Ms4a6c, Ms4a7, Apobec1, Lyz2, Mrc1, Tmem221, Tlr8, Lilrb4a, Msr1, Nnt, and Wdfy1 and a downregulation of Siglech, Slc2a5, and Ccl21a/b. We demonstrate that irradiation and long-term (similar to 6 months) engraftment of the CNS by monocytes induces brain regiondependent alterations in transcription profiles, astrocytes, neuronal structures, including synaptic components, and cognition. Although our results show that microglial replacement with peripherally derived myeloid cells is feasible and that irradiationinduced changes can be reversed by the replacement of microglia with monocytes in the hippocampus, we also observe that brain-wide engraftment of peripheral myeloid cells (relying on irradiation) can result in cognitive and synaptic deficits. Conclusions These findings provide insight into better understanding the role and complexity of myeloid cells in the brain, including their regulation of other CNS cells and functional outcomes.