A Genetic Model of Constitutively Active Integrin CD11b/CD18.

ABSTRACT: Pharmacological activation of integrin CD11b/CD18 (α_Mβ₂, Mac-1, and CR3) shows anti-inflammatory benefits in a variety of animal models of human disease, and it is a novel therapeutic strategy. Reasoning that genetic models can provide an orthogonal and direct system for the mechanistic study of CD11b agonism, we present in this study, to our knowledge, a novel knock-in model of constitutive active CD11b in mice. We genetically targeted the Itgam gene (which codes for CD11b) to introduce a point mutation that results in the I332G substitution in the protein. The I332G mutation in CD11b promotes an active, higher-affinity conformation of the ligand-binding I/A-domain (CD11b αA-domain). In vitro, this mutation increased adhesion of knock-in neutrophils to fibrino

SUBMITTER: Martinez L 

PROVIDER: S-EPMC7577938 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature