Intracellular β2 integrin (CD11/CD18) interacting partners in neutrophil trafficking

Thome, Sarah; Begandt, Daniela; Pick, Robert; Salvermoser, Melanie und Walzog, Barbara (2018): Intracellular β2 integrin (CD11/CD18) interacting partners in neutrophil trafficking. In: European Journal of Clinical Investigation, Bd. 48, Nr. Suppl. 2

Abstract

Background Neutrophil recruitment during acute inflammation critically depends on the spatial and temporal regulation of beta(2) integrins (CD11/CD18). This regulation occurs by inside-out and outside-in signalling via interaction of cytoplasmic proteins with the intracellular domains of the integrin alpha- and beta-subunits. The underlying molecular mechanisms regulating beta(2) integrins in neutrophils are still incompletely understood. Aim Results This review provides a comprehensive overview of our current knowledge on proteins interacting with the cytoplasmic tail of CD18, the conserved beta-subunit of beta(2) integrins, their regulation and their functional importance for neutrophil trafficking during acute inflammation. A total of 22 proteins including Talin, Kindlin 3 and Coronin 1A have been reported to interact with the CD18 cytoplasmic tail. Here, proteins binding to the cytoplasmic domain of CD18 in experiments using purified, recombinant proteins or peptides in, for example, pull-down assays, are defined as direct interactors. Proteins that have been shown to interact with the cytoplasmic domain of CD18 using whole cell lysates in, for example, pull-down experiments are claimed as interacting proteins without evidence for direct interaction. In summary, beta(2) integrin activation and signalling depend on a specific subset of proteins interacting with CD18 and their precise regulation. If disturbed, profound defects of neutrophil recruitment and activation become evident compromising the innate immune response. Conclusions The knowledge of proteins interacting with beta(2) integrins and their regulation during neutrophil trafficking does not only improve our basic understanding of innate immunity but may pave the way to novel therapeutic strategies in the treatment of inflammatory diseases.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0014-2972
• Sprache: Englisch