Linked Life Data

15181284

Source:http://linkedlifedata.com/resource/pubmed/id/15181284

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2004-6-7
pubmed:abstractText
Interaction between Fc receptors expressed on phagocytic cells and antibodies play a critical role in innate immune response. Interestingly, immune cells such as neutrophils, monocytes, and dendritic cells (DCs) express multiple Fc receptors for IgG (FcgammaR) with overlapping ligand specificity. These receptors compete for the same ligand on the target and are known to transduce positive and negative signals to the same cell, depending on presence of type of signaling motif in their cytoplasmic domain. Neutrophils, the first line of defense against bacterial infection and the major phagocytic cell in the blood, express two types of FcgammaRs depending on the species. In humans, the neutrophils co-express immunoreceptor tyrosine-based activation motif (ITAM) containing CD32A and glycosyl-phosphatidyl inositol (GPI)-anchored CD16B, which is in contrast to co-expression of ITAM containing CD16A and ITIM containing CD32B in mouse neutrophils. Recent studies in gene knockout mice have demonstrated that the negative signaling by CD32B plays a critical role in preventing immune complex (IC)-mediated autoimmune diseases by regulating the activation signal delivered by CD16A. However, it is not known how the function of ITAM signaling CD32A is regulated in human neutrophils. Recent observations from our laboratory suggest that in human neutrophils, the CD32A receptor is regulated at the ligand-binding stage. Using a CD16B-deficient donor, we found that the CD32A expressed on resting neutrophils is unable to bind ligand; however, once neutrophils are activated with fMLP, a bacterial chemotactic peptide, the CD32A is functionally active in binding ligand. We also observed that this regulation is neutrophil-specific phenomenon. These observations suggest that FcgammaR can be regulated by distinct mechanisms and factors such as membrane-anchoring, cell-specific signaling, and avidity modulation that may be coordinately involved in regulating the function of human FcgammaR. Because neutrophils may be activated during infectious and inflammatory diseases, the knowledge of functional regulation of FcgammaR will be useful in designing therapies for many autoimmune diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0257-277X
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Functional regulation of human neutrophil Fc gamma receptors.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Research Building Room 7309, 1639 Pierce Drive, Atlanta, GA 30322, USA. pselvar@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review