Linked Life Data

12962702

Source:http://linkedlifedata.com/resource/pubmed/id/12962702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-9-9
pubmed:abstractText
Neutrophils, a major type of blood leukocytes, are indispensable for host defense of bacterial infections. Directed migration in a gradient of chemotactic stimuli enables these cells to rapidly find the site of infection and destroy the invading pathogens. Chemotactic factors bind to seven-transmembrane-domain receptors and activate heterotrimeric G-proteins. Downstream of these proteins a complex interrelated signaling network is activated in human neutrophils. Stimulation of phospholipase C beta results in activation of protein kinase C isoforms and increases in cytosolic calcium. Activation of the enzyme phosphoinositide 3-kinase results in increased production of phosphatidylinositol 3,4,5-trisphosphate and phosphatidyl 3,4-bisphosphate. In addition, small GTP-binding proteins of the Rho family, the mitogen-activated protein kinase cascade, tyrosine kinases and protein phosphatases are activated. The enzyme phosphoinositide 3-kinase and the small cytosolic GTP-binding proteins Rho and Rac emerge as key regulators of neutrophil migration. A steep internal gradient of phosphatidylinositol 3,4,5-trisphosphate, with a high concentration in the leading lamellae, is thought to regulate polarized actin polymerization and formation of protrusions, together with Rac which may be more directly involved in initiating actin reorganization. Rho may regulate localized myosin activation, tail retraction, cell body traction and dynamics of adhesion. The impact of these different signaling pathways on reversible actin polymerization, development of polarity, reversible adhesion and migration, and the putative targets of these pathways in neutrophils, are reviewed in this article. Insight into mechanisms regulating migration of neutrophils could potentially lead to novel therapeutic strategies for counteracting chronic activation of neutrophils which leads to tissue damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1357-2725
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1619-38
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Signaling to migration in neutrophils: importance of localized pathways.
pubmed:affiliation
Department of Pathology, University of Bern, CH-3010 Bern, Switzerland. niggli@patho.unibe.ch
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't