| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, University of Louisville School of Medicine, Health Sciences Center, Louisville, KY 40292
Recent studies have described the development of distinct functional subsets of macrophages in association with cancer, autoimmune disease, and chronic infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing activities in macrophages, it has been proposed that macrophages develop into either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative to the concept of subset development, we propose that macrophages, in response to changes in their tissue environment, can reversibly and progressively change the pattern of functions that they express. As demonstrated herein, macrophages can reversibly shift their functional phenotype through a multitude of patterns in response to changes in cytokine environment. Macrophages display distinct functional patterns after treatment with IFN-
, IL-12, IL-4, or IL-10 and additional functional patterns are displayed depending on whether the cytokine is present alone or with other cytokines and whether the cytokines are added before or concomitantly with the activating stimulus (LPS). Sequential treatment of macrophages with multiple cytokines results in a progression through multiple functional phenotypes. This ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment. A concept of functional adaptivity is proposed that has important implications for therapeutic targeting of macrophages in chronic diseases that result in the dominance of particular functional phenotypes of macrophages that play a significant role in disease pathology.
This article has been cited by other articles:
|
|
 |
|
  R. D. Stout, S. K. Watkins, and J. Suttles Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages J. Leukoc. Biol., November 1, 2009; 86(5): 1105 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Kigerl, J. C. Gensel, D. P. Ankeny, J. K. Alexander, D. J. Donnelly, and P. G. Popovich Identification of Two Distinct Macrophage Subsets with Divergent Effects Causing either Neurotoxicity or Regeneration in the Injured Mouse Spinal Cord J. Neurosci., October 28, 2009; 29(43): 13435 - 13444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sorio and P. Melotti Editorial: The role of macrophages and their scavenger receptors in cystic fibrosis J. Leukoc. Biol., September 1, 2009; 86(3): 465 - 468. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Zaharoff, B. S. Hoffman, H. B. Hooper, C. J. Benjamin Jr., K. K. Khurana, K. W. Hance, C. J. Rogers, P. A. Pinto, J. Schlom, and J. W. Greiner Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12 Cancer Res., August 1, 2009; 69(15): 6192 - 6199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Maldonado-Arocho and K. A. Bradley Anthrax Edema Toxin Induces Maturation of Dendritic Cells and Enhances Chemotaxis towards Macrophage Inflammatory Protein 3{beta} Infect. Immun., May 1, 2009; 77(5): 2036 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Mylonas, M. G. Nair, L. Prieto-Lafuente, D. Paape, and J. E. Allen Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing J. Immunol., March 1, 2009; 182(5): 3084 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Ortega, M. J. Pecaut, D. S. Gridley, L. S. Stodieck, V. Ferguson, and S. K. Chapes Shifts in bone marrow cell phenotypes caused by spaceflight J Appl Physiol, February 1, 2009; 106(2): 548 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sag, D. Carling, R. D. Stout, and J. Suttles Adenosine 5'-Monophosphate-Activated Protein Kinase Promotes Macrophage Polarization to an Anti-Inflammatory Functional Phenotype J. Immunol., December 15, 2008; 181(12): 8633 - 8641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Lumeng, J. B. DelProposto, D. J. Westcott, and A. R. Saltiel Phenotypic Switching of Adipose Tissue Macrophages With Obesity Is Generated by Spatiotemporal Differences in Macrophage Subtypes Diabetes, December 1, 2008; 57(12): 3239 - 3246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nonaka, M. Saio, T. Suwa, A. B. Frey, N. Umemura, H. Imai, G.-F. Ouyang, S. Osada, M. Balazs, R. Adany, et al. Skewing the Th cell phenotype toward Th1 alters the maturation of tumor-infiltrating mononuclear phagocytes J. Leukoc. Biol., September 1, 2008; 84(3): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Hughes, S. Srinivasan, K. R. Lynch, R. L. Proia, P. Ferdek, and C. C. Hedrick Sphingosine-1-Phosphate Induces an Antiinflammatory Phenotype in Macrophages Circ. Res., April 25, 2008; 102(8): 950 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Garrett, K. Dietzmann-Maurer, L. Song, and K. E. Sullivan Polarization of Primary Human Monocytes by IFN-{gamma} Induces Chromatin Changes and Recruits RNA Pol II to the TNF-{alpha} Promoter J. Immunol., April 15, 2008; 180(8): 5257 - 5266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Potts and S. K. Chapes Functions of C2D macrophage cells after adoptive transfer J. Leukoc. Biol., March 1, 2008; 83(3): 602 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Battaglia, S. Delfino, E. Merello, M. Puppo, R. Piva, L. Varesio, and M. C. Bosco Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B J. Leukoc. Biol., March 1, 2008; 83(3): 648 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. MacKinnon, S. L. Farnworth, P. S. Hodkinson, N. C. Henderson, K. M. Atkinson, H. Leffler, U. J. Nilsson, C. Haslett, S. J. Forbes, and T. Sethi Regulation of Alternative Macrophage Activation by Galectin-3 J. Immunol., February 15, 2008; 180(4): 2650 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Flynn and G. Mulcahy Possible Role for Toll-Like Receptors in Interaction of Fasciola hepatica Excretory/Secretory Products with Bovine Macrophages Infect. Immun., February 1, 2008; 76(2): 678 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Joshi, T. Raymond, A. L. Coelho, S. L. Kunkel, and C. M. Hogaboam A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone marrow-derived macrophages to Toll-like receptor agonists J. Leukoc. Biol., February 1, 2008; 83(2): 314 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-S. Chiang, F.-H. Chen, J.-H. Hong, P.-S. Jiang, H.-L. Huang, C.-C. Wang, and W. H. McBride Functional phenotype of macrophages depends on assay procedures Int. Immunol., February 1, 2008; 20(2): 215 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Stearman, L. Dwyer-Nield, M. C. Grady, A. M. Malkinson, and M. W. Geraci A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment Cancer Res., January 1, 2008; 68(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weng, D. Huntley, I-F. Huang, O. Foye-Jackson, L. Wang, A. Sarkissian, Q. Zhou, W. A. Walker, B. J. Cherayil, and H. N. Shi Alternatively Activated Macrophages in Intestinal Helminth Infection: Effects on Concurrent Bacterial Colitis J. Immunol., October 1, 2007; 179(7): 4721 - 4731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strauss-Ayali, S. M. Conrad, and D. M. Mosser Monocyte subpopulations and their differentiation patterns during infection J. Leukoc. Biol., August 1, 2007; 82(2): 244 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-M. Kuang, Y. Wu, N. Chen, J. Cheng, S.-M. Zhuang, and L. Zheng Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes Blood, July 15, 2007; 110(2): 587 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. van Rooijen, A. Plonquet, R. K. Gherardi, and B. Chazaud Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis J. Exp. Med., May 14, 2007; 204(5): 1057 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Weaver, P. A. Pioli, K. Wardwell, S. N. Vogel, and P. M. Guyre Up-regulation of human monocyte CD163 upon activation of cell-surface Toll-like receptors J. Leukoc. Biol., March 1, 2007; 81(3): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Watkins, N. K. Egilmez, J. Suttles, and R. D. Stout IL-12 Rapidly Alters the Functional Profile of Tumor-Associated and Tumor-Infiltrating Macrophages In Vitro and In Vivo J. Immunol., February 1, 2007; 178(3): 1357 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Edwards, X. Zhang, K. A. Frauwirth, and D. M. Mosser Biochemical and functional characterization of three activated macrophage populations J. Leukoc. Biol., December 1, 2006; 80(6): 1298 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kumar and R. Jack Invited review: Origin of monocytes and their differentiation to macrophages and dendritic cells Innate Immunity, October 1, 2006; 12(5): 278 - 284. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Pestka and H.-R. Zhou Toll-Like Receptor Priming Sensitizes Macrophages to Proinflammatory Cytokine Gene Induction by Deoxynivalenol and Other Toxicants Toxicol. Sci., August 1, 2006; 92(2): 445 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Yimin and M. Kohanawa A Regulatory Effect of the Balance between TNF-{alpha} and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice J. Immunol., July 1, 2006; 177(1): 642 - 650. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
