Role of the lectin domain of Mac-1/CR3 (CD11b/CD18) in regulating intercellular adhesion

Abstract

Leukocyte diapedesis requires that Mac-1/CR3-dependent adhesion be regulated so that cells can move from one attachment site to another. The high affinity adhesion state of Mac-1/CR3 is generated when it forms a lectin-dependent complex with the receptor for urokinase plasminogen activator (uPAR; CD87). The extensively glycosylated uPAR binds to the same C-terminal lectin domain of CD11b that had previously been shown to prime Mac-1/CR3 for cytotoxic degranulation in response to beta-glucan. uPAR and beta-glucan compete for a lectin site that is near to the CBRM1/23 epitope (residues 943-1047) at the C-terminus of CD11b, and thus the lectin domain is critical to both the adhesion and cytotoxic functions of Mac-1/CR3. Adhesion is reversed when the uPA enzyme is captured by its receptor (uPAR), causing uPAR to bind to CD11b at a second site (residues 424-440) that is in between the N-terminal I-domain and the divalent cation binding region.