Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response1

Blood monocytes are well-characterized precursors for macrophages and dendritic cells. Subsets of human monocytes with differential representation in various disease states are well known. In contrast, mouse monocyte subsets have been characterized minimally. In this study we identify three subpopulations of mouse monocytes that can be distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and CD62L. The subsets share the characteristics of extensive phagocytosis, similar expression of M-CSF receptor (CD115), and development into macrophages upon M-CSF stimulation. By eliminating blood monocytes with dichloromethylene-bisphosphonate-loaded liposomes and monitoring their repopulation, we showed a developmental relationship between the subsets. Monocytes were maximally depleted 18 h after liposome application and subsequently reappeared in the circulation. These cells were exclusively of the Ly-6Chigh subset, resembling bone marrow monocytes. Serial flow cytometric analyses of newly released Ly-6Chigh monocytes showed that Ly-6C expression on these cells was down-regulated while in circulation. Under inflammatory conditions elicited either by acute infection with Listeria monocytogenes or chronic infection with Leishmania major, there was a significant increase in immature Ly-6Chigh monocytes, resembling the inflammatory left shift of granulocytes. In addition, acute peritoneal inflammation recruited preferentially Ly-6Cmed-high monocytes. Taken together, these data identify distinct subpopulations of mouse blood monocytes that differ in maturation stage and capacity to become recruited to inflammatory sites.

[1]  Steffen Jung,et al.  Blood monocytes consist of two principal subsets with distinct migratory properties. , 2003, Immunity.

[2]  N. Hogg,et al.  Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. , 2003, Blood.

[3]  M. Lutz,et al.  Developmental stages of myeloid dendritic cells in mouse bone marrow. , 2003, International immunology.

[4]  P. Hertzog,et al.  Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c+ DC1 precursors. , 2003, Blood.

[5]  Timothy Ravasi,et al.  The mononuclear phagocyte system revisited , 2002, Journal of leukocyte biology.

[6]  Yong‐jun Liu,et al.  Mouse and human dendritic cell subtypes , 2002, Nature Reviews Immunology.

[7]  T. Rainer L-selectin in health and disease. , 2002, Resuscitation.

[8]  Steffen Jung,et al.  Inflammatory Chemokine Transport and Presentation in HEV , 2001, The Journal of experimental medicine.

[9]  H. Drexhage,et al.  Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes‐prone rat , 2001, Journal of leukocyte biology.

[10]  M. Ernst,et al.  Heterogeneity of human peripheral blood monocyte subsets , 2001, Journal of leukocyte biology.

[11]  N. Van Rooijen,et al.  A critical role for alveolar macrophages in elicitation of pulmonary immune fibrosis , 2000, Immunology.

[12]  Bolund,et al.  Characterization of Murine Dendritic Cells Derived from Adherent Blood Mononuclear Cells In Vitro , 2000, Scandinavian journal of immunology.

[13]  R. Steinman,et al.  Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. , 1999, Immunity.

[14]  C. Figdor,et al.  Generation and functional characterization of mouse monocyte‐derived dendritic cells , 1999, European journal of immunology.

[15]  C. Albanesi,et al.  Cross-linking of membrane CD43 mediates dendritic cell maturation. , 1999, Journal of immunology.

[16]  K. Schmid,et al.  Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and their precursors. , 1998, Journal of leukocyte biology.

[17]  J. Abkowitz,et al.  Mature monocytic cells enter tissues and engraft. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Barth,et al.  The Roman god Janus: a paradigm for the function of CD43. , 1998, Immunology today.

[19]  S. Nishikawa,et al.  Macrophage lineage cells in inflammation: characterization by colony-stimulating factor-1 (CSF-1) receptor (c-Fms), ER-MP58, and ER-MP20 (Ly-6C) expression. , 1998, Blood.

[20]  I. Bakker-Woudenberg,et al.  Bone marrow cellular composition in Listeria monocytogenes infected mice detected using ER-MP12 and ER-MP20 antibodies: a flow cytometric alternative to differential counting. , 1998, Journal of immunological methods.

[21]  D. Klatzmann,et al.  Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover. , 1998, Journal of immunology.

[22]  E. Faist,et al.  Functional analysis of monocyte subsets in surgical sepsis. , 1997, The Journal of trauma.

[23]  M. D. de Bruijn,et al.  High‐level expression of the ER‐MP58 antigen on mouse bone marrow hematopoietic progenitor cells marks commitment to the myeloid lineage , 1996, European journal of immunology.

[24]  I. Weissman,et al.  Flow cytometric identification of murine neutrophils and monocytes. , 1996, Journal of immunological methods.

[25]  M. D. de Bruijn,et al.  Distinct mouse bone marrow macrophage precursors identified by differential expression of ER‐MP12 and ER‐MP20 antigens , 1994, European journal of immunology.

[26]  N. Van Rooijen,et al.  Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. , 1994, Journal of immunological methods.

[27]  N. Rooijen,et al.  Macrophage Subset Repopulation in the Spleen: Differential Kinetics After Liposome‐Mediated Elimination , 1989, Journal of leukocyte biology.

[28]  E. Butcher,et al.  Ly‐6C is a monocyte/macrophage and endothelial cell differentiation antigen regulated by interferon‐gamma , 1988, European journal of immunology.

[29]  F. Modabber,et al.  Increased myelopoiesis during Leishmania major infection in mice: generation of 'safe targets', a possible way to evade the effector immune mechanism. , 1986, Clinical and experimental immunology.

[30]  R. van Furth,et al.  Distribution of blood monocytes between a marginating and a circulating pool , 1986, The Journal of experimental medicine.

[31]  R. van Furth,et al.  QUANTITATIVE STUDY ON THE PRODUCTION AND KINETICS OF MONONUCLEAR PHAGOCYTES DURING AN ACUTE INFLAMMATORY REACTION , 1973, The Journal of experimental medicine.

[32]  R. van Furth,et al.  The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. , 1972, Bulletin of the World Health Organization.