Eosinophils adhere to and stimulate replication of lung fibroblasts 'in vitro'.
Eosinophils have been implicated in several disorders associated with the development of fibrosis. This led us to investigate the interactions between eosinophils and fibroblasts in vitro. Adhesion between purified guinea pig peritoneal eosinophils and monolayers of human fetal lung fibroblasts was assessed using the rose bengal dye staining assay. Fibroblast replication was assessed using a colorimetric assay based upon the uptake and subsequent release of methylene blue. Addition of phorbol myristate acetate induced a rapid, time-dependent increase in eosinophil adhesion (127% and 328% over basal adhesion after 10 and 30 min, respectively). Phorbol myristate acetate-induced adhesion was inhibited by the peptides RGDS and GRGDS (48% and 42%, respectively using 1 mM peptide) and by nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism (46% inhibition at 15 microM). In addition, 24 h culture of fibroblast monolayers with interleukin 1 alpha (IL-1 alpha) or tumour necrosis factor alpha (TNF alpha) resulted in enhanced adhesion (10 U/ml IL-1 alpha stimulated adhesion by 55% of control, 500 U/ml TNF alpha by 75% of control). Conditioned media from cultured eosinophils stimulated fibroblast replication in a time-dependent fashion with maximal stimulation at 3 h. In contrast, media from guinea pig peritoneal macrophages in culture did not show such an effect. This study indicates that eosinophils are capable of both adhering to and releasing mitogens for fibroblasts in vitro. These observations suggest that eosinophils have the capacity to play a role in the development of fibrosis in disorders where they have been shown to be present.
Department of Thoracic Medicine, National Heart and Lung Institute, University of London, UK.
A
A
Shock
K F
KF
Rabe
G
G
Dent
R C
RC
Chambers
A J
AJ
Gray
K F
KF
Chung
P J
PJ
Barnes
G J
GJ
Laurent
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D009842:Oligopeptides; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C047981:arginyl-glycyl-aspartic acid