Linked Life Data

2547873

Source:http://linkedlifedata.com/resource/pubmed/id/2547873

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-9-13
pubmed:abstractText
Although prior studies with mAb have defined an endogenous chymotrypsin-like protease in the neutrophil (polymorphonuclear leukocyte (PMN)) membrane that is associated with initiation of superoxide response to inflammatory stimuli, it is not known whether extracellular proteases (in the inflammatory milieu) can also influence PMN activation. This study examined the ability of four neutral proteases: cathepsin G, elastase, chymotrypsin, and trypsin, to modify PMN superoxide response to FMLP, PMA, and arachidonate. In response to 1 microM FMLP, PMN treated with cathepsin G, chymotrypsin, or elastase showed 64%, 60%, and 32% increases, respectively, in superoxide generation when compared with control, untreated cells (p less than 0.05 for each). These increments were dependent on intact enzymatic function of the proteases, were greatest when enzyme and stimulus were added concurrently, and persisted after PMN were washed free of enzyme. Enhancement of superoxide response was not stimulus specific; in response to 10 ng/ml PMA, cells treated with cathepsin G showed a 84%, and elastase a 57%, increase in superoxide generation (p less than 0.05 for both) with a marked reduction in the time required for onset of this response. For cell activation with 80 microM arachidonate, treatment with elastase produced a 180% increase in superoxide production (p less than 0.025). Neutrophils incubated with trypsin demonstrated significant decreases in superoxide response to PMA (-34%, p less than 0.05) and arachidonate (-39%, p less than 0.01). The enzymes themselves were not stimuli for superoxide production nor were they scavengers for superoxide in cellfree system. We conclude that local release of the PMN primary-granule neutral proteases, cathepsin G, and elastase within inflammatory sites can augment neutrophil effector function by up-regulating oxidative response to defined inflammatory stimuli. This autocrine/paracrine function may provide a significant increase in antimicrobial activity, but may also enhance the potential for host tissue injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids, http://linkedlifedata.com/resource/pubmed/chemical/CTSG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin G, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins, http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin, http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations, http://linkedlifedata.com/resource/pubmed/chemical/Muramidase, http://linkedlifedata.com/resource/pubmed/chemical/N-Formylmethionine..., http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Elastase, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1696-702
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Protease-modulation of neutrophil superoxide response.
pubmed:affiliation
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.