Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 5, Pages 1614-1619Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409057102
Keywords
plasmin; scavenger receptor
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Funding
- NCI NIH HHS [CA31799, R01 CA031799] Funding Source: Medline
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The structural integrity of tissue proteins is damaged in processes ranging from remodeling of the extracellular matrix to destruction by microbial pathogens. Leukocytes play a prominent role in tissue surveillance and repair. However, it remains enigmatic what features of structurally decayed proteins prompt recognition by leukocyte cell-surface receptors. Here, we report that adhesion of human neutrophil granulocytes to fibrinogen is greatly increased by plasmin digestion in a mode where alpha(X)beta(2) dominates the integrin-dependent binding. The bacterial protease subtilisin also enhances binding by alpha(X)beta(2). The a(X) ligand binding domain has an unusually high affinity for carboxyl groups, with K-D at approximate to100 muM. Our findings implicate enhanced accessibility of negatively charged residues in structurally decayed proteins as a pattern recognition motif for alpha(X)beta(2) integrin. Comparisons among integrins show relevance of these findings to the large number of ligands recognized by alpha(M)beta(2) and alpha(X)beta(2) but not alpha(L)beta(2). The observations suggest that the pericellular proteolysis at the leading edge of neutrophils not only facilitates passage through the extracellular matrix but also manufactures binding sites for alpha(X)beta(2).
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