Linked Life Data

18211966

Source:http://linkedlifedata.com/resource/pubmed/id/18211966

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-26
pubmed:abstractText
The manuscript presents definitive studies of surfactant protein D (SP-D) in the context of inflammatory lung fluids. The extent of SP-D depletion in bronchoalveolar lavage fluid (BALF) of children affected with cystic fibrosis (CF) is demonstrated to correlate best with the presence of the active neutrophil serine protease (NSP) elastase. Novel C-terminal SP-D fragments of 27 kDa and 11 kDa were identified in patient lavage fluid in addition to the previously described N-terminal, 35-kDa fragment by the use of isoelectrofocusing, modified blotting conditions, and region-specific antibodies. SP-D cleavage sites were identified. In vitro treatment of recombinant human SP-D dodecamers with NSPs replicated the fragmentation, but unexpectedly, the pattern of SP-D fragments generated by NSPs was dependent on calcium concentration. Whereas the 35- and 11-kDa fragments were generated when incubations were performed in low calcium (200 microM CaCl(2)), incubations in physiological calcium (2 mM) with higher amounts of elastase or proteinase-3 generated C-terminal 27, 21, and 14 kDa fragments, representing cleavage within the collagen and neck regions. Studies in which recombinant SP-D cleavage by individual NSPs was quantitatively evaluated under low and high calcium conditions showed that the most potent NSP for cleaving SP-D is elastase, followed by proteinase-3, followed by cathepsin G. These relative potency findings were considered in the context of other studies that showed that active NSPs in CF BALF are in the order: elastase, followed by cathepsin G, followed by proteinase-3. The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
946-55
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease.
pubmed:affiliation
Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural