| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,¶,,,,
* Diabetes Research Centre, School of Medicine and Medical Science, and
School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland;
Proteome Research Centre and
Proteomics Informatics Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland; and
¶ Siemens Research Ireland, Dublin, Ireland
The resolution of inflammation is a dynamically regulated process that may be subverted in many pathological conditions. Macrophage (M
) phagocytic clearance of apoptotic leukocytes plays an important role in the resolution of inflammation as this process prevents the exposure of tissues at the inflammatory site to the noxious contents of lytic cells. It is increasingly appreciated that endogenously produced mediators, such as lipoxins, act as potent regulators (nanomolar range) of the phagocytic clearance of apoptotic cells. In this study, we have investigated the intriguing possibility that apoptotic cells release signals that promote their clearance by phagocytes. We report that conditioned medium from apoptotic human polymorphonuclear neutrophils (PMN), Jurkat T lymphocytes, and human mesangial cells promote phagocytosis of apoptotic PMN by M and THP-1 cells differentiated to a M-like phenotype. This prophagocytic activity appears to be dose dependent, sensitive to the caspase inhibitor zVAD-fmk, and is associated with actin rearrangement and release of TGF-
1, but not IL-8. The prophagocytic effect can be blocked by the formyl peptide receptor antagonist Boc2, suggesting that the prophagocytic factor(s) may interact with the lipoxin A4 receptor, FPRL-1. Using nanoelectrospray liquid chromatography mass spectrometry and immunodepletion and immunoneutralization studies, we have ascertained that annexin-1 and peptide derivatives are putative prophagocytic factors released by apoptotic cells that promote phagocytosis of apoptotic PMN by M[phi] and differentiated THP-1 cells. These data highlight the role of annexin-1 and peptide derivatives in promoting the resolution of inflammation and expand on the therapeutic anti-inflammatory potential of annexin-1.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Health Research Board, Ireland (to C.G.), Enterprise Ireland (to C.G.), The Wellcome Trust (to C.G.), European Union FP6 Funding (LSHM-CT-2004-005033) (to C.G.), Science Foundation Ireland (to M.B.F., A.d.S., K.J.W., G.C.; Grant 02/IN.1/B117), and The Irish Research Council for Science, Engineering, and Technology (to M.S.). This work was funded under the Programme for Research in Third Level Institutions, administered by the Higher Education Authority.
2 Address correspondence and reprint requests to Prof. Catherine Godson, Diabetes Research Centre, School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. E-mail address: catherine.godson{at}ucd.ie
3 Abbreviations used in this paper: M, macrophage; PtdSer, phosphatidylserine; LPC, lysophosphatidylcholine; LX, lipoxin; PVDF, polyvinylidene difluoride; MS, mass spectrometry; LC, liquid chromatography; Nano-LC MS/MS, nanoelectrospray LC MS/MS; FPR, formyl peptide receptor; FPRL-1, FPR-like-1; PMN, polymorphonuclear neutrophil; hMC, human mesangial cell; 8-Br-cAMP, 8-bromoadenosine cAMP; Rp-cAMP, adenosine 3',5'-cyclic monophosphorothioate; PKA, protein kinase A; PI, propidium iodide; MYH9, nonmuscle myosin II heavy chain isoform A; CF, cystic fibrosis.
4 The online version of this article contains supplemental material.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  J. Dalli, L. V. Norling, D. Renshaw, D. Cooper, K.-Y. Leung, and M. Perretti Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles Blood, September 15, 2008; 112(6): 2512 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Martin, M. Perretti, R. J. Flower, and J. L. Wallace Annexin-1 modulates repair of gastric mucosal injury Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G764 - G769. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
