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Mac‐1 activation by external anions, glutamate and glucuronate
Author(s) -
Lomakina Elena B,
Knauf Philip A,
Schultz Joanne B,
Law FoonYee,
McGraw Matthew D,
Waugh Richard E
Publication year - 2007
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.21.6.a1153-a
Subject(s) - integrin , chemistry , chloride channel , glucuronate , biophysics , microbiology and biotechnology , intracellular , chloride , biochemistry , receptor , biology , organic chemistry
Upon neutrophil activation surface integrins change their conformation allowing the cell to firmly adhere to the vessel wall and subsequently transmigrate into the inflamed tissue. The change in integrin affinity can be caused by cytokines, bacterial products, different anions or chemically induced. Experiments with pharmacological agents and low‐chloride media have suggested the possible role for chloride fluxes as part of the signaling process converting integrins from resting to the activated state. We have shown that substituting glutamate or glucuronate for chloride in the media can cause a rapid increase in the binding of monoclonal antibody CBRM1/5, which recognizes the activation epitope of the Mac‐1 integrin. This change is reflected in the functional adhesion assay that shows the increase in neutrophil binding to endothelial ligand ICAM‐1 (intracellular adhesion molecule). A well known chloride channel inhibitor NPPB (5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid) reduces chloride efflux into the media by 75%, but has no effect on the CBRM1/5 binding or adhesion to immobilized ICAM‐1. Thus, changes in external anion composition, but not chloride efflux, are responsible for the activation of the integrin Mac‐1 in low chloride media. These data not only suggest the new role for chloride in an important signaling mechanism, but also provide the experimental means for converting integrins into activated state for a variety of functional studies.