ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space

Abstract

. ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space. Am J Physiol Lung Cell Mol Physiol 291: L200 -L207, 2006. First published February 3, 2006 doi:10.1152/ajplung.00346.2005.-Neutrophil recruitment into lung constitutes a major response to airborne endotoxins. In many tissues endothelial intercellular adhesion molecule-1 (ICAM-1) interacts with lymphocyte function associated antigen-1 (LFA-1) on neutrophils, and this interaction plays a critical role in neutrophil recruitment. There are conflicting reports about the role of ICAM-1 in neutrophil recruitment into lungs. We studied neutrophil recruitment into alveolar space in a murine model of aerosolized LPSinduced lung inflammation. LPS induces at least a 100-fold increase in neutrophil numbers in alveolar space, as determined by flow cytometry of bronchoalveolar lavage fluid. Neutrophil recruitment was reduced by 54% in ICAM-1 null mice and by 45% in LFA-1 null mice. In wild-type mice treated with anti-ICAM-1 and anti-LFA-1 antibodies, there was 51 and 58% reduction in the neutrophil recruitment, respectively. In chimeric mice, generated by the transplantation of mixtures of bone marrows from LFA-1 null and wild-type mice, the normalized recruitment of LFA-1 null neutrophils was reduced by 60% compared with wild-type neutrophils. Neither the treatment of ICAM-1 null mice with a functionblocking antibody to LFA-1 nor the treatment of LFA-1 null mice with anti-ICAM-1 antibody resulted in further reduction in the recruitment compared with untreated ICAM-1 null and LFA-1 null mice. We conclude that ICAM-1 and LFA-1 play critical roles in the recruitment of neutrophils into the alveolar space in aerosolized LPS-induced lung inflammation, and LFA-1 serves as a ligand of ICAM-1 in the lung.

Endothelial P2Y2 receptor regulates LPS-induced neutrophil transendothelial migration in vitro

“…The lack of the major effect of all these molecules may be specific to the TEM models with HUVECs as the distinct types of endothelial cells may exhibit a different kinetics of IL-8 and ICAM-1 production in response to LPS. On the other hand, our results are in agreement with previously reported in vivo data showing for example that ICAM-1 expression in the lung endothelium increases after ~12 h from LPS-challenge (Basit et al, 2006). It is also conceivable that the model used in this work may reflect the situation that takes place in capillaries, where neutrophils are in close contact with endothelial cells, and thus only the change in endothelium permeability and basal expression of IL-8 and ICAM-1 may be sufficient for their extravasation.…”

“…However, a longer stimulation time (24 h; Fig. 6) resulted in further increase in ICAM-1 expression suggesting that this protein plays a more significant role at later stages of neutrophil migration, as previously reported (Basit et al, 2006). In addition, LPS-induced neutrophil TEM did not involve the upregulation of E-selectin expression as the incubation of HUVECs with 50 mM sialic acid did not affect neutrophil migration (data not shown).…”

“…LPS-induced neutrophil TEM can also be activated by ICAM-1 (Becker et al, 2001;Basit et al, 2006). However, the anti-ICAM-1 blocking antibody only slightly decreased LPSinduced neutrophil migration by ~15% (Fig.…”

“…There is compelling evidence that ICAM-1 plays important role in LPS-induced neutrophil migration (Wagner and Roth, 2000;Becker et al, 2001;Basit et al, 2006). Vascular endothelium expresses low levels of ICAM-1 that is upregulated by inflammatory stimuli such as LPS and TNF-alpha (Yan et al, 2002).…”

“…LPS, a cell wall component of Gram-negative bacteria recognized by cells through Toll like receptor 4 (TLR4), is a potent activator of neutrophil TEM (Wagner and Roth, 2000;Lu et al, 2008). Endothelial cells stimulated with LPS exhibit an increased expression of ICAM-1 and activation of Rho kinase (Basit et al, 2006;Essler et al, 2000) which have been shown to play a critical role in LPS-induced neutrophil recruitment in the lungs (Becker et al, 2001;Basit et al, 2006;Tasaka et al, 2005). In addition, LPS can also stimulate either endothelial cells or neutrophils to secrete interleukin 8 (IL-8), a chemokine that has a major role in leukocyte TEM.…”