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Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis

Clark, Ian A., Awburn, Melissa M, Harper, Clive G., Liomba, N. George and Molyneux, Malcolm E (2003) 'Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis'. Malaria Journal, Vol 2, p. 41.

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Abstract

Background: As well as being inducible by haem, haemoxygenase -1 (HO-1) is also induced by interleukin-10 and an anti-inflammatory
prostaglandin, 15d PGJ2, the carbon monoxide thus produced mediating the anti-inflammatory effects of these molecules. The cellular
distribution of HO-1, by immunohistochemistry, in brain, lung and liver in fatal falciparum malaria, and in sepsis, is reported.
Methods: Wax sections were stained, at a 1:1000 dilution of primary antibody, for HO-1 in tissues collected during paediatric autopsies
in Blantyre, Malawi. These comprised 37 acutely ill comatose patients, 32 of whom were diagnosed clinically as cerebral malaria and the
other 5 as bacterial diseases with coma. Another 3 died unexpectedly from an alert state. Other control tissues were from Australian
adults.
Results: Apart from its presence in splenic red pulp macrophages and microhaemorrhages, staining for HO-1 was confined to intravascular
monocytes and certain tissue macrophages. Of the 32 clinically diagnosed cerebral malaria cases, 11 (category A) cases had negligible
histological change in the brain and absence of or scanty intravascular sequestration of parasitized erythrocytes. Of these 11 cases, eight
proved at autopsy to have other pathological changes as well, and none of these eight showed HO-1 staining within the brain apart from
isolated moderate staining in one case. Two of the three without another pathological diagnosis showed moderate staining of scattered
monocytes in brain vessels. Six of these 11 (category A) cases exhibited strong lung staining, and the Kupffer cells of nine of them were
intensely stained. Of the seven (category B) cases with no histological changes in the brain, but appreciable sequestered parasitised
erythrocytes present, one was without staining, and the other six showed strongly staining, rare or scattered monocytes in cerebral
vessels. All six lung sections not obscured by neutrophils showed strong staining of monocytes and alveolar macrophages, and all six
available liver sections showed moderate or strong staining of Kupffer cells. Of the 14 (category C) cases, in which brains showed microhaemorrhages
and intravascular mononuclear cell accumulations, plus sequestered parasitised erythrocytes, all exhibited strong monocyte
HO-1 staining in cells forming accumulations and scattered singly within cerebral blood vessels. Eleven of the available and readable 13 lung
sections showed strongly staining monocytes and alveolar macrophages, and one stained moderately. All of the 14 livers had strongly
stained Kupffer cells. Of five cases of comatose culture-defined bacterial infection, three showed a scattering of stained monocytes in
vessels within the brain parenchyma, three had stained cells in lung sections, and all five demonstrated moderately or strongly staining
Kupffer cells. Brain sections from all three African controls, lung sections from two of them, and liver from one, showed no staining for
HO-1, and other control lung and liver sections showed few, palely stained cells only. Australian-origin adult brains exhibited no staining,
whether the patients had died from coronary artery disease or from non-infectious, non-cerebral conditions
Conclusions: Clinically diagnosed 'cerebral malaria' in children includes some cases in whom malaria is not the only diagnosis with the
hindsight afforded by autopsy. In these patients there is widespread systemic inflammation, judged by HO-1 induction, at the time of death,
but minimal intracerebral inflammation. In other cases with no pathological diagnosis except malaria, there is evidence of widespread
inflammatory responses both in the brain and in other major organs. The relative contributions of intracerebral and systemic host
inflammatory responses in the pathogenesis of coma and death in malaria deserve further investigation.

Item Type: Article
Additional Information: Published: 19 November 2003. 13 pages (page numbers not for citation purposes. The electronic version of this article is the complete one and can be found online at: http://www.malariajournal.com/content/2/1/41
Uncontrolled Keywords: TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; OXYGENASE-1 GENE PROMOTER; NF-KAPPA-B; HEME OXYGENASE-1; CEREBRAL MALARIA; CARBON-MONOXIDE; FACTOR-ALPHA; SERUM-LEVELS; EXPRESSION
Subjects: ?? R1 ??
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1186/1475-2875-2-41
Related URLs:
Depositing User: Ms Julia Martin
Date Deposited: 07 Jul 2008 09:31
Last Modified: 09 Aug 2017 01:02
URI: https://archive.lstmed.ac.uk/id/eprint/962

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