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

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 significant 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.

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

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 subtupes 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 increased was associated with a significant 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 taht 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.

Evoluçäo das lesöes induzidas por micobactérias BCG e por H37RV em hamster (Mesocricetus auratus) / Evoution of the injuries induced by BCG mycobacterium and by H37RV in hamster (Mesocricetus auratus)

Foram investigados experimentalmente alguns aspectos da patogenia da tuberculose através da inoculaçao de uma cepa de micobactéria de virulência atenuada - BCG e outra cepa altamente virulenta - M. tuberculosis H37 Rv no tecido sub-epitelial do coxim plantar e no tecido sub-epitelial do terço distal da bolsa cervical de hamster, um sítio desprovido de drenagem linfática. A inoculaçao desses agentes determinou diferentes perfis de evoluçao das lesoes, sendo que as lesoes produzidas pelo BCG na pata apresentaram uma tendência de declínio do tamanho após 21 dias e as lesoes produzidas pelo H37 Rv mostraram uma evoluçao progressiva. O mesmo perfil foi observado nas lesoes induzidas na bolsa cervical por ambos os agentes. Contudo, diferentemente do BCG, o H37 Rv disseminou-se para os órgaos internos, causando extensas lesoes. A inoculaçao de BCG ou H37 Rv na pata provocou um aumento de 21 e 68 vezes, respectivamente, o peso do linfonodo satélite em relaçao ao controle, evidenciado a disseminaçao do bacilo por via linfática. Todavia, quando essas amostras foram inoculadas na bolsa, nao determinaram significativas mudanças de peso do linfonodo cervical, mas evidenciou-se a disseminaçao do bacilo virulento por via sangüínea, pelas lesoes produzidas no baço e pulmao.