| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Immunology and
Pharmacology, University of Washington, Seattle, WA 98195
Recruitment of monocytes into tissues and their differentiation into macrophages or dendritic cells (DCs) depend on the microenvironment of the inflammatory site. Although many factors affecting this process have been identified, the intracellular signaling pathways implicated are poorly understood. We found that cyclic nucleotides regulate certain steps of monocyte differentiation into DCs. Increased levels of the cyclic nucleotides, cAMP or cGMP, inhibit differentiation of CD14+/CD1alow monocytes into CD14-/CD1ahigh DCs. However, DC-specific ICAM-3-grabbing nonintegrin (CD209) up-regulation was not affected by cyclic nucleotides, indicating that DC development was not blocked at the monocyte stage. Interestingly, Ag-presenting function was increased by cyclic nucleotides, as measured by the higher expression of MHC class II, CD86, and an increased ability to stimulate CD4+ T cell proliferation in allogeneic MLRs. Although cyclic nucleotides do not completely block DC differentiation, they do block the ability of DCs to be induced to mature by LPS. Treatment during DC differentiation with either cAMP or cGMP analogues hampered LPS-induced expression of CD83, DC-LAMP, and CCR7 and the ability of DCs to migrate toward CCL19/macrophage-inflammatory protein 3
. Interestingly, the induction of a CD16+ subpopulation of cells was also observed. Thus, signals causing an increase in either cAMP or cGMP levels during monocyte recruitment to inflammatory sites may restrain the activation of acquired immunity by blocking DC development and migration to lymph nodes. At the same time, these signals promote development of an active intermediate cell type having properties between those of macrophages and DCs, which might contribute to the innate immune response in the periphery.
This article has been cited by other articles:
|
|
 |
|
  E. Ibeas, L. Fuentes, R. Martin, M. Hernandez, and M. L. Nieto Secreted phospholipase A2 type IIA as a mediator connecting innate and adaptive immunity: new role in atherosclerosis Cardiovasc Res, January 1, 2009; 81(1): 54 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Novitskiy, S. Ryzhov, R. Zaynagetdinov, A. E. Goldstein, Y. Huang, O. Y. Tikhomirov, M. R. Blackburn, I. Biaggioni, D. P. Carbone, I. Feoktistov, et al. Adenosine receptors in regulation of dendritic cell differentiation and function Blood, September 1, 2008; 112(5): 1822 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Colmone, S. Li, and C.-R. Wang Activating Transcription Factor/cAMP Response Element Binding Protein Family Member Regulated Transcription of CD1A J. Immunol., November 15, 2006; 177(10): 7024 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Chen, H. Floyd, N. E. Olson, D. Magaletti, C. Li, K. Draves, and E. A. Clark Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production Blood, February 15, 2006; 107(4): 1459 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Giordano, D. M. Magaletti, and E. A. Clark Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19 Blood, February 15, 2006; 107(4): 1537 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Bender and J. A. Beavo PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte PNAS, January 10, 2006; 103(2): 460 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Bender, C. L. Ostenson, E. H. Wang, and J. A. Beavo Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation PNAS, January 11, 2005; 102(2): 497 - 502. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
