Monocyte migration through the alveolar epithelial barrier: adhesion molecule mechanisms and impact of chemokines.
Alveolar monocyte influx requires adherence and transmigration through the vascular endothelium, extracellular matrix, and alveolar epithelium. For investigating the monocyte migratory process across the epithelial barrier, we employed both the A549 cell line and isolated human alveolar epithelial cells. Under baseline conditions, spontaneous bidirectional transepithelial monocyte migration was noted, which was dose-dependently increased in the presence of the monocyte chemoattractant protein-1. TNF-alpha stimulation of the alveolar epithelium provoked the polarized apical secretion of monocyte chemoattractant protein-1 and RANTES and up-regulation of ICAM-1 and VCAM-1 expression, accompanied by markedly enhanced transepithelial monocyte traffic in the basal-to-apical direction. Multiple adhesive interactions were noted to contribute to the enhanced monocyte traffic across the TNF-alpha-stimulated alveolar epithelium: these included the beta 2 integrins CD11a, CD11b, CD11c/CD18, the beta 1 integrins very late Ag (VLA)-4, -5, and -6, and the integrin-associated protein CD47 on monocytes, as well as ICAM-1, VCAM-1, CD47, and matrix components on the epithelial side. In contrast, spontaneous monocyte migration through unstimulated epithelium depended predominantly on CD11b/CD18 and CD47, with some additional contribution of VLA-4, -5, and -6. In summary, unlike transendothelial monocyte traffic, for which beta 1 and beta 2 integrins are alternative mechanisms, monocyte migration across the alveolar epithelium largely depends on CD11b/CD18 and CD47 but required the additional engagement of the beta 1 integrins for optimal migration. In response to inflammatory challenge, the alveolar epithelium orchestrates enhanced monocyte traffic to the apical side by polarized chemokine secretion and up-regulation of ICAM-1 and VCAM-1.
Rosseau
S
S
Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany. simone.rosseau@innere.med.uni-giessen.de
Selhorst
J
J
Wiechmann
K
K
Leissner
K
K
Maus
U
U
Mayer
K
K
Grimminger
F
F
Seeger
W
W
Lohmeyer
J
J
D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018925:Chemokines; D018836:Inflammation Mediators