Stimulation of both human bronchial epithelium and neutrophils is needed for maximal interactive adhesion.
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.
Bloemen
P G
PG
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Van den Tweel
M C
MC
Henricks
P A
PA
Engels
F
F
Van de Velde
M J
MJ
Blomjous
F J
FJ
Nijkamp
F P
FP
D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation; D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; C065289:ICAM2 protein, human; C483616:ICAM3 protein, human; D018799:Intercellular Adhesion Molecule-1