| 1. |
- Sawesi, Osama, et al.
(författare)
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Serglycin-independent release of active mast cell proteases in response to Toxoplasma gondii infection
- 2010
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:49, s. 38005-38013
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies identified serglycin proteoglycan and its heparin chains to be important for storage and activity of mast cell proteases. However, the importance of serglycin for secretion and activity of mast cell proteases in response to parasite infection has been poorly investigated. To address this issue, we studied the effects on mast cell proteases in serglycin-deficient and wild type mice after peritoneal infection with the obligate intracellular parasite Toxoplasma gondii. In line with previous results, we found severely reduced levels of cell-bound mast cell proteases in both noninfected and infected serglycin-deficient mice. However, serglycin-deficient mice secreted mast cell proteases at wild type levels at the site of infection, and enzymatic activities associated with mast cell proteases were equally up-regulated in wild type and serglycin-deficient mice 48 h after infection. In both wild type and serglycin-deficient mice, parasite infection resulted in highly increased extracellular levels of glycosaminoglycans, including hyaluronan and chondroitin sulfate A, suggesting a role of these substances in the general defense mechanism. In contrast, heparan sulfate/heparin was almost undetectable in serglycin-deficient mice, and in wild type mice, it was mainly confined to the cellular fraction and was not increased upon infection. Furthermore, the heparan sulfate/heparin population was less sulfated in serglycin-deficient than in wild type mice indicative for the absence of heparin, which supports that heparin production is dependent on the serglycin core protein. Together, our results suggest that serglycin proteoglycan is dispensable for normal secretion and activity of mast cell proteases in response to peritoneal infection with T. gondii.
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| 2. |
- Sawesi, Osama
(författare)
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The response of mast cells and serglycin-dependent proteases to parasitic infection : studies on mast cells during Toxoplasma gondii (murine) and Dictyocaulus vivparus (bovine) infection
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The proteoglycan (PG), serglycin (SG), is expressed in several hematopoietic cells and studies of the SG knockout mice (SG-/-) revealed prominent effects on the storage of certain mouse mast cell proteases (mMCPs) such as mMCP-4, -5 and -6.In this thesis, the role of SGPG during parasitic infection was addressed. Both SG+/+ and SG-/- animals infected with Toxoplasma gondii had significantly elevated levels of hyaluronan and chondroitin sulfate A PG in the peritoneum. In contrast, whereas heparin/heparan sulfate was confined to the peritoneal cells in SG+/+ animals, it was almost undetectable in SG-/- animals. Surprisingly, both SG+/+ and SG-/- animals were shown to secrete active MC proteases to almost the same levels in the peritoneal cavity, despite defective storage of proteases in SG-/- MCs. Furthermore, SG-/- animals showed a delayed neutrophil recruitment and decreased levels of proinflammatory cytokines such as IL-6, IL-12, TNF-a and MCP-1. In vitro stimulation of peritoneal derived MCs (PCMCs) with soluble Toxoplasma antigen induced significantly lower secretion of IL-6, IL-12 and TNF-a in SG-/- PCMCs than in SG+/+ PCMCs. In addition, when studying aging SG-/- animals, the deficiency manifested as enlargements of lymphoid tissues, particularly spleens, Peyer’s patches and bronchus associated lymphoid tissue, and was not shown to be associated with infection. Analysis of this phenomenon revealed an expansion of naïve lymphocytes through an increase in the CD4+ and CD45RC+ leukocyte population. Moreover, peritoneal macrophages were markedly increased in number in aging SG-/- animals. In response to Dictyocaulus viviparus infection in calves, tryptase positive MCs in the bovine lung and BALF were shown to correlate with disease progression. The activity and expression levels of tryptase were increased in the lungs of infected calves compared to non-infected control animals. In conclusion, MCs are actively involved in the host response to Toxoplasma gondii infection in mice and Dictyocaulus viviparus infection in calves.
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