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

Published online before print May 8, 2003

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0103037v1 73/6/702    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hamilton, J. A. Search for Related Content PubMed PubMed Citation Articles by Hamilton, J. A.

© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0103037

Received for publication January 22, 2003.
Revised March 3, 2003.
Accepted for publication March 4, 2003.

Article

Nondisposable materials, chronic inflammation, and adjuvant action

Arthritis and Inflammation Research Centre and Cooperative Research Centre for Chronic Inflammatory Diseases, University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Parkville, Australia

	Abstract

Why inflammatory responses become chronic and how adjuvants work remain unanswered. Macrophage-lineage cells are key components of chronic inflammatory reactions and in the actions of immunologic adjuvants. One explanation for the increased numbers of macrophages long term at sites of chronic inflammation could be enhanced cell survival or even local proliferation. The evidence supporting a unifying hypothesis for one way in which this macrophage survival and proliferation may be promoted is presented. Many materials, often particulate, of which macrophages have difficulty disposing, can promote monocyte/macrophage survival and even proliferation. Materials active in this regard and which can initiate chronic inflammatory reactions include oxidized low-density lipoprotein, inflammatory microcrystals (calcium phosphate, monosodium urate, talc, calcium pyrophosphate), amyloidogenic peptides (amyloid and prion protein), and joint implant biomaterials. Additional, similar materials, which have been shown to have adjuvant activity (alum, oil-in-water emulsions, heat-killed bacteria, CpG oligonucleotides, methylated bovine serum albumin, silica), induce similar responses. Cell proliferation can be striking, following uptake of some of the materials, when macrophage-colony stimulating factor is included at low concentrations, which normally promote mainly survival. It is proposed that if such responses were occurring in vivo, there would be a shift in the normal balance between cell survival and cell death, which maintains steady-state, macrophage-lineage numbers in tissues. Thus, there would be more cells in an inflammatory lesion or at a site of adjuvant action with the potential, following activation and/or differentiation, to perpetuate inflammatory or antigen-specific, immune responses, respectively.

Key Words: macrophage survival • oxidized LDL • alum • M-CSF • CSF-1

This article has been cited by other articles:

				K. M. Irvine, C. J. Burns, A. F. Wilks, S. Su, D. A. Hume, and M. J. Sweet A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations FASEB J, September 1, 2006; 20(11): 1921 - 1923. [Abstract] [Full Text] [PDF]

				E. M Cunha, M. J. R Oliveira, P. G Ferreira, and A. P Aguas Mercury intake by inflammatory phagocytes: in vivo cytology of mouse macrophages and neutrophils by X-ray elemental microanalysis coupled with scanning electron microscopy Human and Experimental Toxicology, September 1, 2004; 23(9): 447 - 453. [Abstract] [PDF]