Serglycin-independent release of active mast cell proteases in response to Toxoplasma gondii infection.

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.

• Authors: Osama Sawesi, Dorothe Spillmann, Anna Lundén, Sara Wernersson, Magnus Åbrink
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 49 Pg. 38005-13 (Dec 03 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 20864536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proteoglycans
• Vesicular Transport Proteins
• serglycin
• Heparin
• Heparitin Sulfate
• Peptide Hydrolases

Topics

• Animals
• Gene Expression Regulation, Enzymologic (genetics)
• Heparin (genetics, metabolism)
• Heparitin Sulfate (genetics, metabolism)
• Mast Cells (metabolism)
• Mice
• Mice, Knockout
• Peptide Hydrolases (metabolism)
• Proteoglycans (genetics, metabolism)
• Time Factors
• Toxoplasma (metabolism)
• Toxoplasmosis (genetics, metabolism)
• Up-Regulation (genetics)
• Vesicular Transport Proteins (genetics, metabolism)