Intercellular Adhesion Molecule-1 Mediates Cellular Cross-Talk between Parenchymal and Immune Cells after Lipopolysaccharide Neutralization

Abstract

The mechanisms by which parenchymal cells interact with immune cells, particularly after removal of LPS, remain unknown. Lung explants from rats, mice deficient in the TNF gene, or human lung epithelial A549 cells were treated with LPS and washed, before naive alveolar macrophages, bone marrow monocytes, or PBMC, respectively, were added to the cultures. When the immune cells were cocultured with LPS-challenged explants or A549 cells, TNF production was greatly enhanced. This was not affected by neutralization of LPS with polymyxin B. The LPS-induced increase in the expression of ICAM-1 on A549 cells correlated with TNF production by PBMC. The cellular cross talk leading to the TNF response was blunted by an anti-ICAM-1 Ab and an ICAM-1 antisense oligonucleotide. In A549 cells, a persistent decrease in the concentration of intracellular cAMP was associated with colocalization of LPS into Toll-like receptor 4 and the Golgi apparatus, resulting in increased ICAM-1 expression. Inhibition of LPS internalization by cytochalasin D or treatment with dibutyryl cAMP attenuated ICAM-1 expression and TNF production by PBMC. In conclusion, lung epithelial cells are not bystanders, but possess memory of LPS through the expression of ICAM-1 that interacts with and activates leukocytes. This may provide an explanation for the failure of anti-LPS therapies in sepsis trials.

Diverse macrophage populations mediate acute lung inflammation and resolution

“…During the innate immune response, alveolar macrophages detach from alveolar epithelial cells and secrete more TNF-␣ to stimulate AECs (5,26,163). In response to TNF-␣ or direct Toll-like receptor binding, AECs secrete KC and LPS-induced chemokine (LIX) to recruit PMNs (9,78), secrete MCP-1 to recruit monocytes (143,163,187), and express ICAM-1 and MCP-1 to promote macrophage mobility and phagocytic potential (11,82,100,124,147,162). Viruses with direct epithelial infectivity, such as influenza A, enhance monocyte recruitment by inducing AECs to secrete CCL2 and CCL5 and by facilitating monocyte ␤1 and 2 integrin contact with integrin-associated protein (CD47), ICAM-1, VCAM-1, and junctional adhesion molecule-on the AEC surface (12,63,157).…”

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

“…A549 human alveolar epithelial type 2-like cells (ATCC, Rockville, MD) were maintained as monolayers in DMEM with L-glutamine (Gibco, Grand Island, NY) supplemented with 50 g/mL gentamicin (Gibco) and 10% heat-inactivated fetal bovine serum (complete medium; Gibco). 34 …”

Neutrophils Promote Liver Metastasis via Mac-1–Mediated Interactions with Circulating Tumor Cells

“…A549 human lung carcinoma cells that were obtained within the past 6 months from the American Type Culture Collection were handled as previously described to conduct adhesion assays with isolated human neutrophils. ICAM-1 expression has previously been established in this cell line (39). Circulating neutrophils were isolated on a Ficollhypaque gradient (VWR) from anesthetized C57BL6 mice after cardiac puncture using a heparinized syringe as previously described.…”