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β 2 INTEGRIN COMPLEMENT RECEPTOR 3 (CR3, CD11b/CD18) REGULATION OF NEUTROPHIL FUNCTION
Author(s) -
Byrd Angel S.,
Morin Nicole A.,
Lavigne Liz M.,
Reichner Jonathan S.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.568.2
Subject(s) - ic3b , integrin alpha m , integrin , cd18 , microbiology and biotechnology , complement receptor , receptor , chemotaxis , complement system , signal transduction , chemistry , cell adhesion , biochemistry , biology , cell , immunology , antibody
Complement receptor 3 (CR3, CD11b/CD18) is a β 2 integrin that is unique among integrins in that it contains a polysaccharide binding lectin‐like domain (LLD), in addition to the conventional binding domain (I‐domain). The ligands for the I‐domain are many, such as iC3b, ICAM‐1, fibronectin and fibrinogen. The LLD is a polysaccharide binding site to which a structure known as beta (β) (1‐3) D‐glucan can bind. A number of neutrophil functions have been shown to be altered, including adhesion, diapedesis, chemotaxis and cytotoxicity, depending on single or dual ligation of CR3. Our goals are to analyze downstream signaling pathways once the I‐domain alone is bound; once the LLD alone is bound; once both domains are bound. We hypothesize that single or dual ligation of CR3 will result in stimulation of different intracellular pathways, determining the character of the cell. Experiments will be done using neutrophils isolated from human blood and stimulated with antibodies or ligands directed against the I‐domain and/or LLD. Once the domain specific stimuli have been thoroughly distinguished, mass spectrometric analysis will be done to analyze downstream signaling pathways upon binding of individual or both domains. Ultimately, these studies are expected to render new signaling pathways for CR3. These various pathways will provide fundamental targets for anti‐inflammatory pharmacological therapies.