Matrix metalloproteinase-2 and -9 in the granulomatous fibrosis of rats infected withAngiostrongylus cantonensis

Abstract

The histomorphology of granuloma formation and gelatinase production were investigated in the brains, hearts, lungs and livers of Sprague-Dawley rats infected with Angiostrongylus cantonensis. The relationships between two gelatinases and granulomatous fibrosis were explored, following infection of each rat with 60 infective larvae of the nematode. Worm recovery from the brain was maximal on day 15 post-inoculation whereas peak recovery from the lungs was maximal 75 days later, on day 90. The granulomatous reactions and fibrosis were marked in the lungs but only mild, if present at all, in the brain, heart and liver. Gelatin zymography revealed that matrix metalloproteinase2 (MMP-2) was present, at all time-points, in the heart and lungs, although only in the lungs was there partial conversion of the 72-kDa pro-enzyme to the 64-kDa active form during granulomatous fibrosis. The activity of the MMP-9 pro-enzyme was significantly higher at the time-points when granuloma formation was observed than at other times. Immuno-histochemistry revealed MMP-2 and MMP-9 within the lung granulomas, around infiltrating leucocytes and the epithelial cells of the alveoli. As the granulomatous fibrosis appeared to be strongly associated with MMP-2 and MMP-9, these enzymes may be useful markers in the lungs of rats infected with A. cantonensis.

The paradox of matrix metalloproteinases in infectious disease

“…MMP-9 is detected in the CSF of patients with HTLV-1-induced neurological disease [49]. Astrocytes stimulated by HTLV-1-activated CD4 + T lymphocytes secrete increased MMP-3 and MMP-9, mediated through both soluble factor and integrin- [111,112] dependent pathways [50]. Increased MMP-9 expression is demonstrated in neural cells in the perivascular space in biopsies from patients with HTLV-1 infection and neurological disease, implicating MMP-9 in the local breakdown of the blood-brain barrier [50].…”

Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted

“…Gelatin zymography revealed that the active forms of MMP2 and MMP9 during granulomatous fibrosis are significantly higher than at other times during a 90-day infestation in rats (109). It remains unclear whether the presence of these gelatinases is critical to the confinement of the worm infestation, which would provide a mechanism for natural defense against the infection.…”

“…MMP2 and MMP9 are also implicated in host defense against Angiostrongylus cantonensis, a parasitic worm infestation that causes granulomatous fibrosis reactions in the lung (109). Gelatin zymography revealed that the active forms of MMP2 and MMP9 during granulomatous fibrosis are significantly higher than at other times during a 90-day infestation in rats (109).…”

Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection

“…In this study, immunolocalization of MMP‐9 was demonstrated in multinucleated giant cells and also in mononuclear cells with macrophage and lymphocyte morphologies present in granulomas of P. brasiliensis‐ infected mice. MMP‐9 positivity in macrophages (Hsu et al. 2005) and giant cells (González et al.…”