Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis.

Abstract

Abstract. Focal extracellular matrix degradation morphologically identified in human portal pipestem fibrosis due to Schistosoma mansoni did not express immunohistochemical reactivity for metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). However, when active schistosomal periovular granulomas were present, a strong reactivity for MMP-1, MMP-2, TIMP-1, and TIMP-2 was observed. No reactivity was ever observed for MMP-9. However, the positive pattern of immunohistochemical expression was not seen in old fibrotic periovular granulomas, which were sometimes situated in other areas of the same microscopic section. Positive staining for MMPs and TIMPs was observed at the same time in hepatocytes and within the apical portion of bile duct epithelium. These findings are consistent with the concept that matrix degradation in recent and old fibroses, in addition to differing at the ultrastructural level, also differs in immunohistochemical expression of metalloproteinases and their inhibitors.Extracellular matrix degradation occurs in several physiologic and pathologic conditions. In human portal fibrosis due to schistosomiasis, resorption of fibrous tissue may be quite impressive, since a large amount of hepatic fibrosis can disappear a few years following curative chemotherapy.

Contribution to the study of collagen degradation

“…Ultrastructural findings were, likewise, essentially similar in both groups and at their point intervals. The overall picture was consistent with the process of chronic collagen degradation, as seen in other experimental models (4,11) and in long standing fibrosis of man (1,5,12).…”

“…The morphology of collagen degradation markedly differs when recent and old fibroses are in the process of being removed, as observed in experimental hepatic schistosomiasis of mice (3,4) and during the involution of the Seyle´s inflammatory pouch in rats (11). These differences, also observed on hepatosplenic schistosomiasis of man (1,5,12), have led to the suggestion that the mechanisms operating in acute and chronic collagen degradation may also differ, since morphology and function are closely related. Most experimental models used for the study of extra-cellular matrix degradation (metamorphosis of the tadpole tail, the carrageenin granuloma, involution of the pregnant rat uterus, treated acute schistosomiasis, etc) are representatives of the acute type of degradation.…”

Induction of matrix metalloproteinase-9 in mice during Toxocara canis larvae migration

“…This is in agreement with previous findings in experimental models and patients with bacterial, viral, fungal or parasitic infection (Paul et al 1998;Beuche et al 2000;Leppert et al 2000;Matsuura et al 2000;Vaillant et al 2001). MMP-9 was expressed in schistosomal parasitic infections with hepatic fibrosis (Gomez et al 1999;Vaillant et al 2001).…”

Maternal Infection with Schistosoma japonicum Induces a Profibrotic Response in Neonates

“…All of these markers were evaluated in cord blood from pregnancies with and without maternal schistosome infection. Each of the 10 schistosome-associated profibrotic proteins identified in this report has been associated with fibrosis in children and nonpregnant adults with schistosomiasis (9,(25)(26)(27). However, the elevation of these markers in neonates is remarkable, because there is no evidence for vertical transmission of schistosomiasis japonica in humans, despite its occurrence in other mammals with very different placental morphology (28).…”