Leukadherin 1 is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1 (1). Complement receptor 3 (CR3, CD11b/CD18) is a cell surface receptor expressed on myeloid and natural killer cells (2).
leukadherin 1 is an activator of cd11b/cd18 [1].cd11b/cd18 is a cell surface adhesion receptor that mediates immune functions and leukocyte migration and is expressed primarily in the cells of the innate immune system.leukadherin 1 is a cd11b/cd18 activator. leukadherin 1 increased cd11b/cd18-dependent cell adhesion to fibrinogen with ec50 value of 4 μm [1]. leukadherin 1 increased cd11b/cd18-dependent cell adhesion to its ligand icam-1. in k562 cells, leukadherin 1 increased the binding of cd11b/cd18 to icam-1 through the formation of long membrane tethers [2].in the acute peritonitis mice model, leukadherin 1 significantly reduced neutrophil accumulation by 40% [1]. in a mhc mismatched orthotopic kidney transplantation mouse model, leukadherin 1 reduced interstitial leukocyte infiltration, glomerular damage, neointimal hyperplasia and prolonged survival from 48.5% (csa only) to 100% (csa and la1) [3]. in newborn rats exposed to hyperoxia (85% o2), leukadherin 1 reduced both macrophage and neutrophil infiltration in the lungs [4].
[1]. maiguel d, faridi mh, wei c, et al. small molecule-mediated activation of the integrin cd11b/cd18 reduces inflammatory disease. sci signal, 2011, 4(189): ra57.
[2]. celik e1, faridi mh, kumar v, et al. agonist leukadherin-1 increases cd11b/cd18-dependent adhesion via membrane tethers. biophys j, 2013, 105(11): 2517-2527.
[3]. khan sq, guo l, cimbaluk dj, et al. a small molecule b2 integrin agonist improves chronic kidney allograft survival by reducing leukocyte recruitment and accompanying vasculopathy. front med (lausanne), 2014, 1: 45.
[4]. jagarapu j, kelchtermans j, rong m, et al. leukadherin-1 attenuates hyperoxia-induced lung injury in neonatal rats. am j respir cell mol biol, 2015.
