Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity

Abstract

Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the β integrins lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Here, we identify coronin 1A (Coro1A) as a novel regulator of β integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and postadhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high-affinity LFA-1 in focal zones of adherent cells. Defective integrin affinity regulation in the genetic absence of impairs leukocyte adhesion and extravasation in inflamed cremaster muscle venules in comparison with control animals. In a mouse infection model, PMN infiltration into the gastric mucosa is dramatically reduced in mice, resulting in an attenuated gastric inflammation. Thus, Coro1A represents an important novel player in integrin biology, with key functions in PMN trafficking during innate immunity.

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

“…Pull‐down experiments using lysates of neutrophil‐like differentiated HL‐60 cells and subsequent mass spectrometry reveal an interaction of Coronin 1A with CD18 . Further pull‐down assays using peptides of the cytoplasmic tail of CD18 and primary human neutrophil lysates confirmed the interaction between Coronin 1A and CD18, although experimental evidence for direct interaction remains elusive . Coronin 1A is required for induction of adhesion in murine neutrophils under physiological flow conditions by regulating LFA‐1 affinity.…”

“…The actin‐binding protein Coronin 1A is predominantly expressed in leukocytes and involved in cytoskeleton‐associated processes including cell polarization and migration . Pull‐down experiments using lysates of neutrophil‐like differentiated HL‐60 cells and subsequent mass spectrometry reveal an interaction of Coronin 1A with CD18 . Further pull‐down assays using peptides of the cytoplasmic tail of CD18 and primary human neutrophil lysates confirmed the interaction between Coronin 1A and CD18, although experimental evidence for direct interaction remains elusive .…”

“…41 Further pull-down assays using peptides of the cytoplasmic tail of CD18 and primary human neutrophil lysates confirmed the interaction between Coronin 1A and CD18, although experimental evidence for direct interaction remains elusive. 41 Coronin 1A is required for induction of adhesion in murine neutrophils under physiological flow conditions by regulating LFA-1 affinity. In addition, Coronin 1A also regulates Mac-1 affinity and influences neutrophil adhesion strengthening, spreading, 2D migration and their accumulation at sites of inflammation highlighting its importance for integrin regulation.…”

“…Coronin 1A is required for induction of adhesion in murine neutrophils under physiological flow conditions by regulating LFA‐1 affinity. In addition, Coronin 1A also regulates Mac‐1 affinity and influences neutrophil adhesion strengthening, spreading, 2D migration and their accumulation at sites of inflammation highlighting its importance for integrin regulation …”

“…In addition, Coronin 1A also regulates Mac-1 affinity and influences neutrophil adhesion strengthening, spreading, 2D migration and their accumulation at sites of inflammation highlighting its importance for integrin regulation. 41 The GEF Cytohesin 1 catalyses the replacement of GDP by GTP and regulates ADP ribosylation factor (ARF)-GTPases. 42 Cytohesin 1 is predominantly expressed in tissues of hematopoietic origin and represents a direct interactor of CD18 in pull-down experiments.…”