A relevant enzyme in granulomatous reaction, active matrix metalloproteinase-9, found in bovine Echinococcus granulosus hydatid cyst wall and fluid

Abstract

In addition to the ability of matrix metalloproteinases (MMP) to degrade components of the extracellular matrix and their involvement in pathology-related processes of tissue remodeling, they were recently reported to enhance inflammation by activation of proinflammatory cytokines, or their release from the cell surface. In the work reported here, proteolytic activity previously found for hydatid cysts was further characterized as MMP-9. Active host MMP-9 was found in walls and fluids of bovine hydatid cysts of Echinococcus granulosus in the environment of granulomatous reaction. Pooled walls and fluids of hydatid cysts obtained from infected cattle were processed. Strong proteolytic activity was detected by zymography. The proteolytic fraction was purified by anion exchange and gelatin-agarose affinity chromatography. Major proteinases of the purified fraction were subjected to mass spectrometry and their identities were further confirmed by Western blotting using commercial anti-human MMP-9 monoclonal antibodies. Two proteinases were characterized as latent and active forms of host MMP-9. Using the same antibody for immunoblot, activity was localized, in paraffin-embedded sections of the parasite and the local host environment, to epithelioid and giant multinucleated cells. It is proposed here that MMP-9 is secreted by specialized host cells of monocytic lineage (epithelioid/giant cells) as an effector, in an attempt to digest the persistent foreign body. In vivo activation of MMP-9 suggests its involvement in inflammatory reaction and in the chemotaxis of inflammatory cells to the cyst. However, E. granulosus can deal efficiently with MMP-9. Research is suggested into possible immune evasion mechanisms, including the secretion of an inhibitory molecule.

Echinococcus multilocularisand Its Intermediate Host: A Model of Parasite-Host Interplay

“…Host immunoglobulins and albumin [48, 49, 51, 52], activators and inhibitors of the complement cascade [50, 53] and, recently, host-derived active matrix metalloproteinase 9, which was assumed to play a role in the periparasitic granulomatous reactions [54], were found in Echinococcus sp. hydatid fluid or bound to the cyst wall.…”

How echinoccocosis affects potential cancer markers in plasma: galectin-3, sN-cadherin and sE-cadherin? a preliminary report

“…in endothelial cells, lymphocytes and macrophages. Furthermore, the expression of certain MMPs and plasminogen activators is also increased in liver cells during liver regeneration [19,20]. …”

“…MMP-9 [19,30]. Discriminant analysis revealed that the association of two or more markers significantly increased their efficiency.…”

Echinococcosis

“…Effector mechanisms include neutrophils and macrophage activation, nitric oxide (NO), eosinophil cationic protein, complement, and antibodies (Virginio et al 2007;Amri et al 2007;Ferreira et al 2000a;Heath et al 1994;Jenkins et al 1990;Ramos et al 2006;Ferragut and Nieto 1996;Severi et al 1997;Zhang et al 2003b;Riley et al 1986;Dempster et al 1992). Around live intact cysts there is a remarkably scarce inflammatory reaction, as opposed to regressive cysts (Breijo et al 2008;Coltorti and Varela-Diaz 1974;Marco et al 2006;Sakamoto and Cabrera 2003). Although it is not clear whether the inflammatory reaction is the cause of cyst inactivation or the consequence of hydatid cyst fluid (HCF) spillage from spontaneously damaged cysts, some evidence exists that cysts can be damaged by an early pericystic inflammatory reaction (Fotiadis et al 1999).…”

“…Each viable protoscolex (PSC) may develop into an adult worm if ingested by a definitive host or into a new cyst if disseminated in tissues of an intermediate host as the consequence of cyst rupture (secondary hydatidosis). Around intact cysts there is a remarkably scarce inflammatory reaction (Breijo et al 2008;Coltorti and Varela-Diaz 1974;Marco et al 2006;Sakamoto and Cabrera 2003).…”