The Authors Reply

Abstract

We thank Rogacev et al.1.Rogacev K. Zawada A. Heine G. CKD-associated atherosclerosis and moncyte heterogeneity.Kidney Int. 2012; 81: 599Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar for their interest in our mini review ‘Novel Inflammatory Mechanisms of Accelerated Atherosclerosis in Kidney Disease.’2.Swaminathan S. Shah S.V. Novel inflammatory mechanisms of accelerated atherosclerosis in kidney disease.Kidney Int. 2011; 80: 453-463Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar While we appreciate and acknowledge the important points raised by the authors regarding homology of monocyte heterogeneity between mice and humans, we suggest several additional aspects that are worth considering. Although we agree that Gr1+/Ly6Chi are pro-inflammatory monocytes and are putative homologs of human CD14+CD16- monocytes, in many settings, depending on local and systemic cues, they can also differentiate into a variety of macrophage and dendritic cell (DC) subtypes that could inhibit immune response.3.Geissmann F. Manz M.G. Jung S. et al.Development of monocytes, macrophages, and dendritic cells.Science. 2010; 327: 656-661Crossref PubMed Scopus (2174) Google Scholar Pertaining to atherosclerosis, although Ly6Chi monocytes more efficiently accumulate in atherosclerotic plaques, Ly6Clo anti-inflammatory monocytes were particularly prone to developing into plaque cells that express the DC marker CD11c.4.Tacke F. Alvarez D. Kaplan T.J. et al.Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques.J Clin Invest. 2007; 117: 185-194Crossref PubMed Scopus (1009) Google Scholar Similarly, in human atheroma, macrophages express c-fms (macrophage colony-stimulating factor receptor) but not inflammatory cytokines such as interleukin-6,5.Salomon R.N. Underwood R. Doyle M.V. et al.Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma.Proc Natl Acad Sci USA. 1992; 89: 2814-2818Crossref PubMed Scopus (111) Google Scholarand CD14+CD16- rather than CD16+ monocytes correlate with worse myocardial salvage after myocardial infarction.6.Tsujioka H. Imanishi T. Ikejima H. et al.Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction.J Am Coll Cardiol. 2009; 54: 130-138Abstract Full Text Full Text PDF PubMed Scopus (294) Google Scholar More recently, gene expression profiling has identified close similarities between murine and human monocyte subsets in more than 100 genes, suggesting similarity between Ly6Chi monocytes and human CD14+CD16- monocytes, and between Ly6Clo anti-inflammatory mouse monocytes and CD16+ human monocytes.7.Ingersoll M.A. Spanbroek R. Lottaz C. et al.Comparison of gene expression profiles between human and mouse monocyte subsets.Blood. 2010; 115: e10-e19Crossref PubMed Scopus (495) Google Scholar This has led the authors to refer to monocytes as CD14+CD16- and CD16+ subsets in both species. However, it is important to point out some notable differences that the authors observed between the homologous human and mouse monocyte subsets, especially in PPAR-γ and phagocytic receptor expression. Thus, origin, differentiation, and plasticity of different monocyte subsets in mice, and the corresponding cell populations in humans and their independent role in health and disease, remain to be fully elucidated.