Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granule proteins play a major role in bacterial killing by neutrophils. Serglycin proteoglycan, the major intracellular proteoglycan of hematopoietic cells, has been proposed to play a role in sorting and packing of granule proteins. We examined the content of major neutrophil granule proteins in serglycin knockout mice and found neutrophil elastase absent from mature neutrophils as shown by activity assay, Western blotting, and immunocytochemistry, whereas neutrophil elastase mRNA was present. The localization of other neutrophil granule proteins did not differ between wild-type and serglycin knockout mice. Differential counts and neutrophil ultrastructure were unaffected by the lack of serglycin, indicating that defective localization of neutrophil elastase does not induce neutropenia itself, albeit mutations in the neutrophil elastase gene can cause severe congenital neutropenia or cyclic neutropenia. The virulence of intraperitoneally injected Gram-negative bacteria (Klebsiella pneumoniae) was increased in serglycin knockout mice compared with wild-type mice, as previously reported for neutrophil elastase knockout mice. Thus, serglycin proteoglycan has an important role in localizing neutrophil elastase in azurophil granules of neutrophils, while localization of other granule proteins must be mediated by other mechanisms.
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PMID:Neutrophil elastase depends on serglycin proteoglycan for localization in granules. 1727 11

Mutations in the neutrophil elastase (NE) gene have been postulated to interfere with normal intracellular trafficking of NE as an AP3-interacting membrane integrated protein and to cause severe congenital or cyclic neutropenia in humans. Here, we show that in U937 promonocytes NE is synthesized as a predominantly soluble proenzyme and is completely secreted in the presence of phorbol esters similarly to serglycin. Using chemical cross-linking NE is shown to be associated with serglycin as 34 kDa proenzyme in the trans-Golgi region of these cells indicating that it is delivered to lysosomes associated with serglycin.
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PMID:Neutrophil elastase is associated with serglycin on its way to lysosomes in U937 cells. 1761 93