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THE HEPATIC EXTRAMEDULLARY HEMATOPOIESIS DURING EXPERIMENTAL MURINE SCHISTOSOMIASIS MANSONI
Granuloma
Ambiente hematopoiético
Angiogênese
Hematopoiese extramedular
Granuloma
Hematopoietic environment
Angiogenesis
Extramedullary hematopoiesis
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia do Brasil em Neuroimunomodulação. Rio de Janeiro, RJ , Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia do Brasil em Neuroimunomodulação. Rio de Janeiro, RJ , Brasil.
Abstract
Many years ago, our research group has demonstrated extramedullary
hematopoiesis in the peripheral zone of murine hepatic schistosomal
granulomas. In the present study, we revisit this phenomenon using new
technical and conceptual approaches. Therefore, newborn mice were
percutaneously infected by Schistosoma mansoni cercariae and euthanized
between 35- and 60-days post infection. Liver samples were submitted to
histopathology and immunohistochemical analyses. Cells under mitosis and/or
expressing Ki67 demonstrated the proliferation of hematopoietic cells both
around the parasite’s eggs trapped in the liver and around hepatic vessels. After
50 days post infection, proliferating cells at different levels on differentiation
were located preferentially in the peripheral zone of the granulomas, around
the vessels and inside the sinusoids. The presence of acidic and sulfated
glycoconjugates, reticular fibers and the absence of fibronectin characterized
the microenvironment for attraction and maintenance of hematopoiesis. Some
neutrophils secreted MMP9 from the earliest points of infection, indicating
degradation of the extracellular matrix in regions of histolysis and a possible
chemoattraction of hematopoietic stem cells to the liver. Fall-3+ cells and Sca-
1+ cells indicated that early hematopoietic progenitors could be mobilized to
the liver. Groups of vWF+ megakaryocytes suggest chemoattraction of these
cells and/or migration, proliferation, and differentiation of very immature
progenitors to this organ. The increase of blood vessels and extramedullary
hematopoiesis in this environment, where markers of immature hematopoietic
and endothelial cells have been identified, points to the possibility of the
presence of progenitors for endothelial and hematopoietic cells in the liver
during the infection. There is also the possibility of concomitant migration of more differentiated hematopoietic progenitors, that proliferate and
differentiate in the liver, and the occurrence of angiogenesis caused by
inflammation or release of ovular antigens that stimulate the activation and
proliferation of endothelial cells. Altogether, these data increase knowledge
about a murine model that is of interest for investigating the pathology of the
schistosomiasis and also the dynamics of hematopoiesis.
Keywords in Portuguese
EsquistossomoseGranuloma
Ambiente hematopoiético
Angiogênese
Hematopoiese extramedular
Keywords
SchistosomiasisGranuloma
Hematopoietic environment
Angiogenesis
Extramedullary hematopoiesis
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