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].
References:
[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.