HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Soruri, A. Articles by Zwirner, J. Search for Related Content PubMed PubMed Citation Articles by Soruri, A. Articles by Zwirner, J.

Anaphylatoxin C5a Induces Monocyte Recruitment and Differentiation into Dendritic Cells by TNF- and Prostaglandin E₂-Dependent Mechanisms ¹

Afsaneh Soruri^*, Joachim Riggert, Thilo Schlott, Ziba Kiafard^*, Claudia Dettmer^* and Jörg Zwirner^2,*

Departments of ^* Immunology, Cytopathology, and Transfusion Medicine, Georg August University Gottingen, Gottingen, Germany

Although monocytes can be directed to develop into dendritic cells (DC) in vitro, the molecular mechanisms that induce their transformation in vivo are largely unknown. In the present study we employed an in vivo SCID mouse model to investigate the impact of two proinflammatory chemotaxins, the anaphylatoxin C5a and the chemokine macrophage inflammatory protein-1 (CCL3), on the differentiation of human monocytes and immature DC generated from monocytes in the presence of GM-CSF and IL-4. Both C5a and macrophage inflammatory protein-1 recruited human monocytes and immature DC into the peritoneal cavity of SCID mice, but only C5a induced their differentiation into phenotypically mature DC by 48 h after injection. Macrophages derived from monocytes by in vitro culture were resistant to C5a-mediated transformation in vivo. The effect of C5a was indirect, since C5a-stimulated TNF- and PGE₂ were found to be obligatory as well as sufficient to induce differentiation of monocytes. In contrast to monocytes, in vitro generated immature DC required TNF-, but not PGE₂, for their C5a-mediated maturation in vivo. C5a-transformed monocytes represented an inflammatory type of DC, as they constitutively secreted high amounts of TNF-, but also retained the capacity to release the Th1 cytokine IL-12 p70 upon stimulation with CD40 ligand. In summary, we identified for the first time a cascade of inflammatory signals that can induce the transformation of monocytes into DC in vivo. This novel function emphasizes the important immunoregulatory role of C5a at the interface of innate and adaptive immunity.

This article has been cited by other articles:

				S. M. Mangsbo, J. Sanchez, K. Anger, J. D. Lambris, K. N. Ekdahl, A. S. Loskog, B. Nilsson, and T. H. Totterman Complement Activation by CpG in a Human Whole Blood Loop System: Mechanisms and Immunomodulatory Effects J. Immunol., November 15, 2009; 183(10): 6724 - 6732. [Abstract] [Full Text] [PDF]

				Y. Nakayama, S.-I. Kim, E. H. Kim, J. D. Lambris, M. Sandor, and M. Suresh C3 Promotes Expansion of CD8+ and CD4+ T Cells in a Listeria monocytogenes Infection J. Immunol., September 1, 2009; 183(5): 2921 - 2931. [Abstract] [Full Text] [PDF]

				P. N. Lalli, M. G. Strainic, F. Lin, M. E. Medof, and P. S. Heeger Decay Accelerating Factor Can Control T Cell Differentiation into IFN-{gamma}-Producing Effector Cells via Regulating Local C5a-Induced IL-12 Production J. Immunol., November 1, 2007; 179(9): 5793 - 5802. [Abstract] [Full Text] [PDF]

				R. A. Moulton, M. A. Mashruwala, A. K. Smith, D. R. Lindsey, R. A. Wetsel, D. L. Haviland, R. L. Hunter, and C. Jagannath Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice J. Leukoc. Biol., October 1, 2007; 82(4): 956 - 967. [Abstract] [Full Text] [PDF]

				C. S. Rinder, M. J. Smith, H. M. Rinder, D. N. Cortright, R. M. Brodbeck, J. E. Krause, and B. R. Smith Leukocyte Effects of C5a-Receptor Blockade During Simulated Extracorporeal Circulation Ann. Thorac. Surg., January 1, 2007; 83(1): 146 - 152. [Abstract] [Full Text] [PDF]

				D. S. Daniel, G. Dai, C. R. Singh, D. R. Lindsey, A. K. Smith, S. Dhandayuthapani, R. L. Hunter Jr, and C. Jagannath The Reduced Bactericidal Function of Complement C5-Deficient Murine Macrophages Is Associated with Defects in the Synthesis and Delivery of Reactive Oxygen Radicals to Mycobacterial Phagosomes J. Immunol., October 1, 2006; 177(7): 4688 - 4698. [Abstract] [Full Text] [PDF]

				E. Kamoshita, Y. Ikeda, M. Fujita, H. Amano, A. Oikawa, T. Suzuki, Y. Ogawa, S. Yamashina, S. Azuma, S. Narumiya, et al. Recruitment of a Prostaglandin E Receptor Subtype, EP3-Expressing Bone Marrow Cells Is Crucial in Wound-Induced Angiogenesis Am. J. Pathol., October 1, 2006; 169(4): 1458 - 1472. [Abstract] [Full Text] [PDF]

				A. Rivas-Carvalho, M. A. Meraz-Rios, L. Santos-Argumedo, S. Bajana, G. Soldevila, M. E. Moreno-Garcia, and C. Sanchez-Torres CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines Int. Immunol., September 1, 2004; 16(9): 1251 - 1263. [Abstract] [Full Text] [PDF]

				A. H. J. Kim, I. D. Dimitriou, M. C. H. Holland, D. Mastellos, Y. M. Mueller, J. D. Altman, J. D. Lambris, and P. D. Katsikis Complement C5a Receptor Is Essential for the Optimal Generation of Antiviral CD8+ T Cell Responses J. Immunol., August 15, 2004; 173(4): 2524 - 2529. [Abstract] [Full Text] [PDF]

				D. Kamei, K. Yamakawa, Y. Takegoshi, M. Mikami-Nakanishi, Y. Nakatani, S. Oh-ishi, H. Yasui, Y. Azuma, N. Hirasawa, K. Ohuchi, et al. Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1 J. Biol. Chem., August 6, 2004; 279(32): 33684 - 33695. [Abstract] [Full Text] [PDF]