S. Rosseau et al., Monocyte migration through the alveolar epithelial barrier: Adhesion molecule mechanisms and impact of chemokines, J IMMUNOL, 164(1), 2000, pp. 427-435
Alveolar monocyte influx requires adherence and transmigration through the
vascular endothelium, extracellular matrix, and alveolar epithelium, For in
vestigating the monocyte migratory process across the epithelial barrier, w
e employed both the A549 cell line and isolated human alveolar epithelial c
ells. Under baseline conditions, spontaneous bidirectional transepithelial
monocyte migration was noted, which was dose-dependently increased in the p
resence of the monocyte chemoattractant protein-1. TNF-alpha stimulation of
the alveolar epithelium provoked the polarized apical secretion of monocyt
e chemoattractant protein-1 and RANTES and up-regulation of ICAM-1 and VCAM
-1 expression, accompanied by markedly enhanced transepithelial monocyte tr
affic in the basal-to-apical direction. Multiple adhesive interactions mere
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, sp
ontaneous monocyte migration through unstimulated epithelium depended predo
minantly on CD11b/CD18 and CD47, with some additional contribution of VLA-4
, -5, and -6, In summary, unlike transendothelial monocyte traffic, for whi
ch beta(1) and beta(2) integrins are alternative mechanisms, monocyte migra
tion 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 chem
okine secretion and up-regulation of ICAM-1 and VCAM-1.