Pediatric Hematopoietic Stem Cell Transplantation for Pharmacists by Carolina Witchmichen Penteado Schmidt

Author:Carolina Witchmichen Penteado Schmidt
Language: eng
Format: epub
ISBN: 9783030434915
Publisher: Springer International Publishing

4.1.3 Homing Second Step: Activation of Lymphocyte Function-Associated Antigen 1 (LFA-1), Very Late Antigen 4/5 (VLA-4/5), and CD44

Lymphocyte Function-Associated Antigen 1 (LFA-1)

The LFA-1 is an integrin receptor that is expressed only by leukocytes . This receptor is involved in every step of the leukocyte-endothelial cell adhesion cascade—which are rolling , firm adhesion , transmigration , and sub-endothelial migration . It also cognates the interactions between T-cells and antigen-presenting cells . Its main ligand is intercellular adhesion molecule-1 (ICAM-1) that is expressed on endothelium , sub-endothelial cells, and leukocytes . The Adhesiveness of LFA-1 is controlled by receptor-transduced signals, as well as by adhesion -strengthening signals emanating from ligand binding. The LFA-1 conformation is then modified, precluding adhesion events in the bloodstream or at sites distant from the inflammatory target. In the inactive form, the LFA-1 α/β heterodimer (CD11a/CD18 ) has a bent conformation, which causes the ligand-binding headpiece less accessible. The active conformation of LFA-1 has an extended structure that exposes the ligand-binding site on the I domain of the α subunit headpiece. The extended conformation is recognized by the reporter antibodies KIM-127 and 24 , and they bind to epitopes from β subunit and α/β headpiece. The switch between active and inactive conformers is controlled by a membrane-proximal motif on the cytoplasmic domain of the β subunit, which competes with the intracytoplasmic region on the α subunit promoting a low-affinity state and also competes with the cytoskeletal protein talin promoting a high-affinity state [14].

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