Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE
<p>Abstract</p> <p>Background</p> <p>It has been shown previously that human monocytes fed with haemozoin (HZ) or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9) enzyme activity and protein/mRNA expression and increased TNF production...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-08-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/7/1/157 |
| _version_ | 1818916397236879360 |
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| author | Giribaldi Giuliana Gallo Valentina Prato Mauro Arese Paolo |
| author_facet | Giribaldi Giuliana Gallo Valentina Prato Mauro Arese Paolo |
| author_sort | Giribaldi Giuliana |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>It has been shown previously that human monocytes fed with haemozoin (HZ) or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9) enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ) and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects.</p> <p>Methods</p> <p>Native HZ freshly isolated from <it>Plasmodium falciparum </it>(Palo Alto strain, Mycoplasma-free), delipidized HZ, beta-haematin (lipid-free synthetic HZ), trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting.</p> <p>Results</p> <p>Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants) and protein/mRNA expression (in cell lysates) of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid) a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator possibly responsible for increase of both IL-1beta production and MMP-9 activity.</p> <p>Conclusion</p> <p>Results indicate that specific lipoperoxide derivatives generated by HZ may play a role in modulating production of IL-1beta and MMP-9 expression and activity in HZ/trophozoite-fed human monocytes. Results may clarify aspects of cerebral malaria pathogenesis, since MMP-9, a metalloproteinase able to disrupt the basal lamina is possibly involved in generation of hallmarks of cerebral malaria, such as blood-brain barrier endothelium dysfunction, localized haemorrhages and extravasation of phagocytic cells and parasitized RBCs into brain tissues.</p> |
| first_indexed | 2024-12-20T00:17:31Z |
| format | Article |
| id | doaj.art-05d17328feb04fd385d5709fa0ded63b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-20T00:17:31Z |
| publishDate | 2008-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-05d17328feb04fd385d5709fa0ded63b2022-12-21T20:00:16ZengBMCMalaria Journal1475-28752008-08-017115710.1186/1475-2875-7-157Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETEGiribaldi GiulianaGallo ValentinaPrato MauroArese Paolo<p>Abstract</p> <p>Background</p> <p>It has been shown previously that human monocytes fed with haemozoin (HZ) or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9) enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ) and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects.</p> <p>Methods</p> <p>Native HZ freshly isolated from <it>Plasmodium falciparum </it>(Palo Alto strain, Mycoplasma-free), delipidized HZ, beta-haematin (lipid-free synthetic HZ), trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting.</p> <p>Results</p> <p>Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants) and protein/mRNA expression (in cell lysates) of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid) a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator possibly responsible for increase of both IL-1beta production and MMP-9 activity.</p> <p>Conclusion</p> <p>Results indicate that specific lipoperoxide derivatives generated by HZ may play a role in modulating production of IL-1beta and MMP-9 expression and activity in HZ/trophozoite-fed human monocytes. Results may clarify aspects of cerebral malaria pathogenesis, since MMP-9, a metalloproteinase able to disrupt the basal lamina is possibly involved in generation of hallmarks of cerebral malaria, such as blood-brain barrier endothelium dysfunction, localized haemorrhages and extravasation of phagocytic cells and parasitized RBCs into brain tissues.</p>http://www.malariajournal.com/content/7/1/157 |
| spellingShingle | Giribaldi Giuliana Gallo Valentina Prato Mauro Arese Paolo Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE Malaria Journal |
| title | Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE |
| title_full | Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE |
| title_fullStr | Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE |
| title_full_unstemmed | Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE |
| title_short | Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE |
| title_sort | phagocytosis of haemozoin malarial pigment enhances metalloproteinase 9 activity in human adherent monocytes role of il 1beta and 15 hete |
| url | http://www.malariajournal.com/content/7/1/157 |
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