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Distorted Secretory Granule Composition in Mast Cells with Multiple Protease Deficiency
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
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2013 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 191, nr 7, s. 3931-3938Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

Ort, förlag, år, upplaga, sidor
2013. Vol. 191, nr 7, s. 3931-3938
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Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-209849DOI: 10.4049/jimmunol.1301441ISI: 000324634500049OAI: oai:DiVA.org:uu-209849DiVA, id: diva2:659913
Anmärkning

G.Calounova and I.Eriksson contributed equally to this work.

Tillgänglig från: 2013-10-28 Skapad: 2013-10-28 Senast uppdaterad: 2017-12-06Bibliografiskt granskad

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Eriksson, IngerTchougounova, ElenaKjellén, Lena

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Eriksson, IngerTchougounova, ElenaKjellén, Lena
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Institutionen för medicinsk biokemi och mikrobiologiInstitutionen för immunologi, genetik och patologi
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