Abstract
The normal course of hematopoiesis is controlled by growth factors and cytokines and, therefore, should be susceptible to alterations induced by systemic mediator release such as that seen following thermal injury. We hypothesized that a brief exposure of developing macrophages to the postthermal injury state would result in functionally altered progeny. We measured the production of inflammatory mediators by rat, bone-marrow macrophage precursors harvested 24 h following a 30% TBSA burn after subsequent maturation in a controlled, in vitro environment. Interleukin (IL)-6, tumor necrosis factor (TNF), and prostaglandin (PG) E2 levels in response to 24 h stimulation with lipopolysaccharide (LPS) were measured following 4 or 8 days of incubation with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or both. Flow cytometric analysis showed that bone marrow cells harvested from burn and sham animals cultured in GM-CSF developed principally into macrophages (His48−, R21A6A+, CD11b+. Unstimulated cells produced negligent levels of cytokines and PGE2. Stimulated burn-derived cells released greater amounts of IL-6 and TNF at 4 or 8 days of culture depending on the conditions. Elevated PGE2 release was noted in all GM-CSF containing cultures, with burn-derived cells showing a trend towards reduced prostaglandin release. Detection of mRNA for cytokines after LPS stimulation showed no change in IL-6 or TNF transcripts. A short exposure to the systemic effects of thermal injury preprogramed macrophage progenitor cells with the propensity to develop into inflammatory macrophages, secreting higher levels of TNF and IL-6. This shift towards proinflammatory functions in these cells suggests they could be a source of enhanced inflammatory mediator release at 4 or more days post thermal injury.
Similar content being viewed by others
REFERENCES
OGLE, C. K., X. GUO, K. SZCZUR, S. HARTMEN, and J. D. OGLE. 1994. Production of tumor necrosis factor, interleukin-6 and prostaglandin E2 by LPS-stimulated rat bone marrow macrophages after thermal injury: Effect of indomethacin. Inflammation 18:175–185.
WU, J., C. K. OGLE, J. MAO, K. SZCZUR, J. E. FISCHER, and J. D. OGLE. 1995. The increased potential for the production of inflammatory cytokines by kupffer cells and splenic macrophages eight days after thermal injury. Inflammation 19:529–541.
NATHAN, C. 1987. Secretory products of macrophages. J. Clin. Invest. 79:319–326.
FALK, L. A., and S. N. VOGEL. 1988. Comparison of bonemarrow progenitors response to granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor. J. Leukoc. Biol. 43:148–157.
FALK, L. A., M. M. HOGAN, and S. N. VOGEL. 1988. Bone marrow progenitors cultured in the presence of granulocyte-macrophage colony-stimulating factor versus colony-stimulating factor differentiate into macrophages with distinct tumoricidal capacities. J. Leukoc. Biol. 43:471–476.
YAMAMOTO, Y., T. W. KLEIN, M. TOMIOKA, and H. FRIEDMAN. 1997. Differential effects of granulocyte/macrophage colony-stimulating factor (GM-CSF) in enhancing macrophage resistance to Legionella pneumophilia vs Candida albicans. Cell. Immunol. 176:75–81.
KELLER, J. R., and J. N. IHLE. 1989. Unique pathway of IL-3-driven hemopoietic differentiation. J. Immunol. 143:4025–4033.
RUTERFORD, M. S., and L. B. SCHOOK. 1992. Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor. J. Leukoc. Biol. 51:69–76.
DEXTER, T. M., and E. SPOONCER. 1987. Growth and differentiation in the hematopoietic system. Annu. Rev. Cell Biol. 3:423–444.
IHLE, J. N. 1989. The molecular and cellular biology of interleukin-3. In The Year in Immunology. Immunoregulatory Cytokines and Cell Growth. J. M. Cruse and R. E. Lewis, Jr., editors. Karger, Basel. 59.
MC NIECE, I. K., F. M. STEWART, D. M. DEACON, and P. J. QUESENBERRY. 1988. Synergistic interactions between hematopoietic growth factors as detected by in vitro mouse bone marrow colony formation. Exp. Hematol. 16:383–388.
METCALF, D., S. MERCHAV, and G. WAGEMAKER. 1982. Commitment by GM-CSF or M-CSF of biopotential GM progenitor cells to granulocyte or macrophage formation. In Experiments in Hematology Today. S. J. Baum, G. D. Ledney, and S. Thierfeldman, editors. S. Karger, Basel. 3–9.
CAUX, C., S. SAELAND, C. FAVRE, V. DUVERT, P. MANNONI, and J. BANCHEREAU. 1990. Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells. Blood 75:2292–2298.
ARIYAMA, Y., S. MISAWA, and Y. SONODA. 1995. Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture. Stem Cells 13:404–413.
STRUZYNA, J., Z. POIDA, B. BRAUN, M. CHOMICKA, E. SOBICZEWSKA, and J. WREMBEL. 1995. Serum cytokine levels (IL-4, IL-6, IL-8, G-CSF, GM-CSF) in burned patients. Burns 21:437–440.
FUKUSHIMA, R., J. W. ALEXANDER, J. Z. WU, J. X. MAO, K. SZCZUR, A. M. STEPHENS, J.D. OGLE, and C. K. OGLE. 1994. Time course of production of cytokines and prostaglandin E2 by macrophages isolated after thermal injury and bacterial translocation. Circ. Shock, 42:154–162.
WU, J., C. K. OGLE, J. E. FISCHER, G. D. WARDEN, and J. D. OGLE. 1995. The mRNA expression and in vitro production of cytokines and other proteins by hepatocytes and Kupffer cells following thermal injury. Shock 3:268–273.
RUFF, M. R., and G. GIFFORD. 1981. Tumor necrosis factor. In Lymphokines, Vol. 2. E. Pick, editor. Academic Press, New York. 235–273.
VANSNICK, J., S. A. CAYPHAS, and A. VINK. 1989. Purification of NH2 terminal amino acid sequence of a T-cell derived lymphokine with growth factor activity for b cell hybridoma. Proc. Natl. Acad. Sci. U.S.A. 3:9679–9683.
SAMBROOK, J., and E. F. FRITSCH. 1989. Molecular cloning, a laboratory manual. Cold Spring Harbor Laboratory Press.
MARTIN, R., C. HOOVER, S. GRIMME, C. GROGAN, J. HOLTKE, and C. KESSLER. 1990. A highly sensitive, nonradioactive DNA labeling and detection system. Biotechniques 9:762–768.
SCHLUTER, B., B. KONIG, U. BERGMAN, F. E. MULLER, and W. KONIG. 1991. Interleukin 6—A potential mediator of lethal sepsis after major thermal trauma: Evidence for increased IL-6 production by peripheral blood mononuclear cells. J. Trauma 31:1663–1669.
CANNON, J. G., J. S. FRIEDBERG, J. A. GELFAND, R. G. TOMPKINS, J. F. BURKE, and C. A. DINARELLO. 1992. Circulating interleukin-1β and tumor necrosis factor-α concentrations after burn injury in humans. Critical Care Medicine 20:1414–1419.
MARANO, M. A., Y. FONG, L. L. MOLDAWER, H. WEI, S. E. CALVANO, K. J. TRACER, P. S. BARIE, K. MANOGUE, A. CERAMI, G. T. SHIRES, and S. F. LOWRY. 1990. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg. Gynecol. and Obstetrics 70:32–38.
UEYAMA, M., I. MARUYAMA, M. OSAME, and Y. SAWADA. 1992. Marked increase in plasma interleukin-6 in burn patients. J. Lab. Clin. Med. 120:693–698.
IKEJIMA, T., S. OKUSAWA, J. W. M.VAN DER MEER, and C. A. DINARELLO. 1988. Induction by toxic-shock-syndrome toxin-1 of a circulating tumor necrosis factor-like substance from human mononuclear cells. J. Infect. Dis. 158:1017–1025.
RUTHERFORD, M. S., and L. B. SCHOOK. 1992. Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor. J. Leukoc. Biol. 51:69–76.
CLARK, S. C., and R. KAMEN. 1987. The human hematopoietic colony-stimulating factors. Science 236:1229–1237.
IKEBUCHI, K., G. G. WONG, S. C. CLARK, J. N. IHLE, Y. HIRAI, and M. OGAWA. 1987. Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotent hemopoietic progenitors. Proc. Natl. Acad. Sci. U.S.A. 84:9035–9039.
ARAI, K., F. LEE, F. MIYAJAMA, S. MIYATAKE, N. ARAI, and T. YAKOTA. 1990. Cytokines: Coordinators of immune and inflammatory responses. Annu. Rev. Biochem. 59:783–836.
BROWN, C. Y., C. A. LAGNADO, M. A. VADAS, and G. J. GOODALL. 1996. Differential regulation of the stability of cytokine nRNAs in lipopolysaccharide-activated blood monocytes in response to IL-10. J. Biol. Chem. 271:20108–20112.
STERNFELD, D. C., C. K. OGLE, J. F. VALENTE, J. G. NOEL, and G. D. WARDEN. 1997. Thermal injury functionally alters bone marrow derived macrophages: A study of monocyte-hepatocyte interactions. J. Burn Care 18:(In press).
SNOECK, H. W., S. WEEKX, A. MOULIJN, F. LARDON, M. LENJOU, G. NYS, P. C. F. VAN RANST, D. R. VAN BOCKSTAELE, and Z. N. BERNEMAN. 1996. Tumor necrosis factor α is a potent synergistic factor for the proliferation of primitive human hematopoietic progenitor cells and induces resistance to transforming growth factor β but not to interferon γ. J. Exp. Med. 183:705–710.
JACOBSEN, S. E. W., F. W. RUSCETTI, A. B. ROBERTS, and J. R. KELLER. 1993. TGF-β is a bidirectional modulator of cytokine receptor expression on murine bone marrow cells. J. Immunol. 151:4534–4544.
KOBAYASHI, M., M. IMAMURA, Y. GOTOHDA, S. MAEDA, H. IWASSAKI, K. SAKURADA, M. KASAI, A. J. HAPEL, and T. MIYAZAKI. 1991. Synergistic effects of interleukin-1β and interleukin-3 on the expansion of human hematopoietic progenitor cells in liquid cultures. Blood 78:1947–1953.
STROBL, H., E. RIEDL, C. SCHEINECKER, C. BELLO-FERNANDEZ, W. F. PICKL, K. RAPPERSBERGER, O. MAJDIC, and W. KNAPP. 1996. TGF-β1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157:1499–1507.
MUENCH, M. O., J. G. SCHNEIDER, and M. A. S. MOORE. 1992. Interactions among colony-stimulating factors, IL-lβ IL-6, and Kit-ligand in the regulation of primitive murine hematopoietic cells. Exp. Hematol. 20:339–349.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogle, C.K., Valente, J.F., Guo, X. et al. Thermal Injury Induces the Development of Inflammatory Macrophages from Nonadherent Bone Marrow Cells. Inflammation 21, 569–582 (1997). https://doi.org/10.1023/A:1027377904641
Issue Date:
DOI: https://doi.org/10.1023/A:1027377904641