High expression of myeloid-related proteins 8 and 14 characterizes an inflammatorily active but ineffective response of macrophages during leprosy

High expression of myeloid-related proteins 8 and 14 characterizes an inflammatorily active but ineffective response of macrophages during leprosy

Author Sunderkotter, C. H. Google Scholar
Tomimori-Yamashita, J. Google Scholar
Nix, V Google Scholar
Maeda, S. M. Google Scholar
Sindrilaru, A. Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Sorg, C. Google Scholar
Roth, J. Google Scholar
Institution Univ Ulm
Univ Munster
Universidade Federal de São Paulo (UNIFESP)
Abstract Macrophages are decisive cells for the course of leprosy as they phagocytose Mycobacterium leprae and have the potential to influence the specific immune response. Expression and release of the myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9) characterize a proinflammatory subtype of macrophage that is prominent in, for example, murine infection with lack of a T helper 1 cell response and in certain highly active chronic inflammations of mice and humans. We investigated cutaneous biopsies of the different forms of leprosy (41 untreated patients) including leprosy reaction type 1 (reversal reaction) and type 2 (erythema nodosum leprosum) (n = 18) for expression of MRP8 and MRP14 by subtypes of macrophages. Concomitantly we determined serum levels of MRP8 and MRP14 by sandwich enzyme-linked immunosorbent assay. Expression of MRP8 and MRP14 by CD68-positive macrophages was low in tuberculoid leprosy and rose significantly in borderline tuberculoid leprosy and especially in multibacillary forms, there being expressed by mycobacteria-loaded foam cells. A significant rise of MRP8 and MRP14 expression also occurred in lepra reactions compared to the corresponding non-reactional forms. in type 2 reactions this additional increase was associated with a sigificant elevation of serum levels. in type 1 it was associated with expression of MRP8 and MRP14 by epitheloid and giant cells, which so far were considered not to express both proteins. in conclusion, we present evidence that the two prominent proteins MRP8 and MRP14 can be re-expressed in vivo by tissue macrophages in chronic infection, that their increased expression is characteristic for a macrophage subtype associated with high inflammatory but low antimycobacterial activity in the absence of a T helper 1 response, and that their significant rise in serum during erythema nodosum leprosum bears diagnostic and pathophysiological relevance.
Language English
Date 2004-04-01
Published in Immunology. Oxford: Blackwell Publishing Ltd, v. 111, n. 4, p. 472-480, 2004.
ISSN 0019-2805 (Sherpa/Romeo, impact factor)
Publisher Blackwell Publishing Ltd
Extent 472-480
Origin http://dx.doi.org/10.1111/j.0019-2805.2004.01836.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000220547100016
URI http://repositorio.unifesp.br/handle/11600/27682

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