Shifts in bone marrow cell phenotypes caused by spaceflight.

Bone marrow cells were isolated from the humeri of C57BL/6 mice after a 13-day flight on the space shuttle Space Transportation System (STS)-118 to determine how spaceflight affects differentiation of cells in the granulocytic lineage. We used flow cytometry to assess the expression of molecules that define the maturation/activation state of cells in the granulocytic lineage on three bone marrow cell subpopulations. These molecules included Ly6C, CD11b, CD31 (platelet endothelial cell adhesion molecule-1), Ly6G (Gr-1), F4/80, CD44, and c-Fos. The three subpopulations were small agranular cells [region (R)1], larger granular cells (R2), which were mostly neutrophils, and very large, very granular cells (R3), which had properties of macrophages. Although there were no composite phenotypic differences between total bone marrow cells isolated from spaceflight and ground-control mice, there were subpopulation differences in Ly6C (R1 and R3), CD11b (R2), CD31 (R1, R2, and R3), Ly6G (R3), F4/80 (R3), CD44(high) (R3), and c-Fos (R1, R2, and R3). In particular, the elevation of CD11b in the R2 subpopulation suggests neutrophil activation in response to landing. In addition, decreases in Ly6C, c-Fos, CD44(high), and Ly6G and an increase in F4/80 suggest that the cells in the bone marrow R3 subpopulation of spaceflight mice were more differentiated compared with ground-control mice. The presence of more differentiated cells may not pose an immediate risk to immune resistance. However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights.

[1]  E. Wagner,et al.  Bone and haematopoietic defects in mice lacking c-fos , 1992, Nature.

[2]  Simon C Watkins,et al.  Association of murine CD31 with transmigrating lymphocytes following antigenic stimulation. , 1992, The American journal of pathology.

[3]  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.

[4]  M W Luttges,et al.  Effects of suspension-induced osteopenia on the mechanical behaviour of mouse long bones , 1991, Journal of materials science. Materials in medicine.

[5]  T. Majima,et al.  Role of macrophage inflammatory protein 2 in acute lung injury in murine peritonitis. , 2002, The Journal of surgical research.

[6]  Louis S Stodieck,et al.  Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions. , 2003, Journal of applied physiology.

[7]  S. Maher,et al.  Ly-6 Superfamily Members Ly-6A/E, Ly-6C, and Ly-6I Recognize Two Potential Ligands Expressed by B Lymphocytes1 , 2002, The Journal of Immunology.

[8]  J. Bach,et al.  In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells. , 2004, Immunology letters.

[9]  J W Armstrong,et al.  The effects of rM-CSF and rIL-6 therapy on immunosuppressed antiorthostatically suspended mice. , 1995, Journal of applied physiology.

[10]  S. Gordon,et al.  Membrane molecules as differentiation antigens of murine macrophages. , 1998, Advances in immunology.

[11]  R. Furth,et al.  THE KINETICS OF PROMONOCYTES AND MONOCYTES IN THE BONE MARROW , 1970 .

[12]  E. Morey,et al.  Spaceflight and Bone Turnover: Correlation with a New Rat Model of Weightlessness , 1979 .

[13]  L S Neale,et al.  Alteration in human mononuclear leucocytes following space flight. , 1992, Immunology.

[14]  M. Tavassoli,et al.  The significance of intramedullary cancellous bone formation in the repair of bone marrow tissue , 1969, The Anatomical record.

[15]  J. Suttles,et al.  Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences1 , 2005, The Journal of Immunology.

[16]  J. Minguell Is hyaluronic acid the "organizer" of the extracellular matrix in marrow stroma? , 1993, Experimental hematology.

[17]  G Sonnenfeld,et al.  Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses. , 1999, Journal of applied physiology.

[18]  B. Girten,et al.  Preventing annoyance from odors in spaceflight: a method for evaluating the sensory impact of rodent housing. , 2003, Journal of applied physiology.

[19]  M. Gordon,et al.  Hyaluronic acid regulates the function and distribution of sulfated glycosaminoglycans in bone marrow stromal cultures. , 1993, Experimental hematology.

[20]  M. D. de Bruijn,et al.  Markers of mouse macrophage development detected by monoclonal antibodies. , 1994, Journal of immunological methods.

[21]  S. Arkins,et al.  The colony-stimulating factors induce expression of insulin-like growth factor-I messenger ribonucleic acid during hematopoiesis. , 1995, Endocrinology.

[22]  Y. Shibata,et al.  Restoration of Prostaglandin Releasing Macrophage Populations in Lethally Irradiated Mice With Spleen Cells From Bone Marrow‐Depleted Donors , 1991, Journal of leukocyte biology.

[23]  E. Wright,et al.  Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling. , 2008, Cancer research.

[24]  A. Hatzfeld,et al.  The heparin binding PECAM-1 adhesion molecule is expressed by CD34+ hematopoietic precursor cells with early myeloid and B-lymphoid cell phenotypes. , 1993, Blood.

[25]  M W Luttges,et al.  Skeletal unloading causes organ-specific changes in immune cell responses. , 1993, Journal of applied physiology.

[26]  M. Wright,et al.  Molecular Cloning of F4/80-Like-Receptor, a Seven-Span Membrane Protein Expressed Differentially by Dendritic Cell and Monocyte-Macrophage Subpopulations1 2 , 2001, The Journal of Immunology.

[27]  G R Taylor,et al.  Immunological analyses of U.S. Space Shuttle crewmembers. , 1986, Aviation, space, and environmental medicine.

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

[29]  Minguell Jj Is hyaluronic acid the "organizer" of the extracellular matrix in marrow stroma? , 1993 .

[30]  T. Curran,et al.  Induction of c-fos during myelomonocytic differentiation and macrophage proliferation , 1985, Nature.

[31]  T. Bateman,et al.  Effects of space flight and IGF-1 on immune function. , 1999, Advances in space research : the official journal of the Committee on Space Research.

[32]  P. Fraker,et al.  Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function , 2008, Proceedings of the National Academy of Sciences.

[33]  R. Ahmed,et al.  Cytotoxic T-cell memory without antigen , 1994, Nature.

[34]  A T Ichiki,et al.  Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells , 1996, Journal of leukocyte biology.

[35]  C. Hermenegildo,et al.  Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice. , 2006, Human reproduction.

[36]  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.

[37]  L. Schwarzfischer,et al.  Comparative analysis of integrin expression on monocyte‐derived macrophages and monocyte‐derived dendritic cells , 2000, Immunology.

[38]  M. Melis,et al.  Murine macrophage precursor characterization. I. Production, phenotype and differentiation of macrophage precursor hybrids , 1990, European journal of immunology.

[39]  R. Ganta,et al.  Mouse infection models for space flight immunology. , 2005, Advances in space biology and medicine.

[40]  P. Johnson,et al.  Regulation of hematopoiesis in rats exposed to antiorthostatic hypokinetic/hypodynamia: II. Mechanisms of the "anemia". , 1986, Aviation, space, and environmental medicine.

[41]  S. Vogel,et al.  Bone marrow-derived macrophages: development and regulation of differentiation markers by colony-stimulating factor and interferons. , 1985, Journal of immunology.

[42]  C. Wade,et al.  Increases in body mass of rats during spaceflight: models and measurements. , 2000, Aviation, space, and environmental medicine.

[43]  Z. Allebban,et al.  Effects of spaceflight on the number of rat peripheral blood leukocytes and lymphocyte subsets , 1994, Journal of leukocyte biology.

[44]  P. Johnson,et al.  Regulation of hematopoiesis in rats exposed to antiorthostatic, hypokinetic/hypodynamia: I. Model description. , 1985, Aviation, space, and environmental medicine.

[45]  X. Holy,et al.  Effects of space food bar feeding on bone mass and metabolism in normal and unloaded rats. , 2002, Nutrition research.

[46]  Q. He,et al.  Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody , 1992, The Journal of experimental medicine.

[47]  O. Simell,et al.  Ly-6C regulates endothelial adhesion and homing of CD8(+) T cells by activating integrin-dependent adhesion pathways. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[48]  V. Perry,et al.  Localization and function of tissue macrophages. , 1986, Ciba Foundation symposium.

[49]  C. Smith,et al.  Quantitation of Intracellular Mac-i (CD1 i b/CDi 8) Pools in Human Neutrophils , 1988 .

[50]  D. Pyatt,et al.  Reactive oxygen species mediate stem cell factor synergy with granulocyte/macrophage colony-stimulating factor in a subpopulation of primitive murine hematopoietic progenitor cells. , 1996, Molecular pharmacology.

[51]  A. Lawler How Much Space for Science? , 2004, Science.

[52]  Michael W. Bungo,et al.  Results of the life sciences DSOs conducted aboard the space shuttle 1981-1986 , 1987 .

[53]  Y. Shibata,et al.  Selectively Eliminated Blood Monocytes and Splenic Suppressor Macrophages in Mice Depleted of Bone Marrow by Strontium 89 , 1985, Journal of leukocyte biology.

[54]  I. Trowbridge,et al.  Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues , 1982, Immunogenetics.

[55]  G R Taylor,et al.  Spaceflight alters immune cell function and distribution. , 1992, Journal of applied physiology.

[56]  Rg Miller,et al.  The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems , 1977, The Journal of experimental medicine.

[57]  G R Taylor,et al.  Effects of spaceflight on levels and activity of immune cells. , 1990, Aviation, space, and environmental medicine.

[58]  Daniel Lucas,et al.  Haematopoietic stem cell release is regulated by circadian oscillations , 2008, Nature.