Stimulation of both human bronchial epithelium and neutrophils is needed for maximal interactive adhesion

Abstract

It has become clear that the bronchial epithelium is not just a passive barrier but plays an active role in inflammation. It can produce several inflammatory mediators and does express cell adhesion molecules of which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analyzed in detail the interaction of neutrophils with human bronchial epithelial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incubated with freshly isolated 51Cr-labeled neutrophils for 30 min at 37 degrees C; then the nonadherent cells were removed by washing gently. Stimulation of the epithelial cells with IFN-gamma or the combination of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) (which doubles the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanine (fMLP), platelet-activating factor, or TNF-alpha also caused a profound enhancement of the adhesion. A significant additional increase was found when the epithelial cells had been exposed to IFN-gamma and the neutrophils were stimulated with fMLP simultaneously. This effect was even more pronounced with epithelium preincubated with IFN-gamma and TNF-alpha. With the use of monoclonal antibodies against CD18 and ICAM-1, it was demonstrated that the increased adhesion was mainly mediated by the ICAM-1/beta 2-integrin interaction. This study highlights that both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactive adhesion.

Fluticasone Propionate Downregulates Nasal Fibroblast Functions Involved in Airway Inflammation and Remodeling

“…ICAM-1 and VCAM-1 expression is enhanced in tissue sites of inflammatory reactions and is associated with leukocyte transmigration over fibroblasts [33, 34]. Increased VCAM-1 expression was recently found in nasal polyp microvascular endothelium, and the proportion of VCAM-1-positive vessels correlated with the number of tissue eosinophils [18].…”

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

“…Ligation of VLA-5 by the FHA RGD domain induces activation of NF-B, which then causes the up-regulation of epithelial intercellular adhesion molecule 1 (ICAM-1) (385,386). ICAM-1 up-regulation is involved in leukocyte accumulation and activation at the site of bacterial infection (59,593,762). Interestingly, purified PT can abrogate NF-B activation by this mechanism, suggesting the involvement of a PT-sensitive G protein in the signaling process (the role of PT is discussed in detail later in this review) (386).…”

Transepithelial Migration of Neutrophils

“…In fact, inflammatory stimuli up-regulate ICAM-1 on the surface of intestinal (25,57,58), conjunctival (57), renal, and bladder (59-61), as well as tracheal (32,33,62), bronchial (31,(63)(64)(65), and alveolar (66, 67) epithelial cells. Furthermore, neutrophil adherence to the apical surface of cultured tracheal (33), bronchial (31,68), and intestinal (58) epithelial cells is ICAM-1 dependent. Finally, ICAM-1 inhibition may have a protective effect in lung injury (69,70) and sepsis (71), although there are conflicting Definition of abbreviations: CAR, coxsackie and adenovirus receptor; ECM, extracellular matrix; ICAM, intercellular adhesion molecule; JAM, junctional adhesion molecule; PECAM, platelet endothelial cell adhesion molecule; PSGL, P-selectin glycoprotein ligand; ZO-1, zonula occludens-1.…”