Silica, hyaluronate, and alveolar macrophage functional differentiation.
BACKGROUND
Silicosis is mediated by macrophages, their soluble mediators, and extracellular matrix molecules. In this study, we investigated the effects of silica and/or hyaluronate (HA) on several alveolar macrophage responses.


METHODS
We evaluated glycosaminoglycan (GAG) production by radiolabeled precursors, nitric oxide (NO) release by its oxidation product, phagocytic activity by Candida albicans internalization, and the secretion of two fibrogenic cytokines, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta, by specific assays.


RESULTS
Silica significantly reduced GAG secretion, particularly HA secretion. Alone, it decreased Candida uptake; associated with HA, it enhanced the reduction. Silica and Candida reduced NO release, which was not significantly affected when silica- or Candida-exposed cells were also treated with HA. TNF-alpha and TGF-beta activities were stimulated by silica but reduced by HA.


CONCLUSIONS
The results suggest that silica and HA modify alveolar macrophage functional differentiation. Silica- and HA-induced modifications of the microenvironment could determine whether the response proceeds toward healing and repair or toward lung chronic pathology.
Bodo
Maria
M
Histology Section, Faculty of Medicine, University of Perugia, Italy. bodo@unipg.it
Bellocchio
Silvia
S
Bellucci
Catia
C
Balloni
Stefania
S
Pietrella
Donatella
D
Sbaraglia
Giovanni
G
Muzi
Giacomo
G
Lilli
Cinzia
C
Lumare
Alessandro
A
Dell'Omo
Marco
M
Abbritti
Giuseppe
G
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006025:Glycosaminoglycans / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004338:Drug Combinations; D006025:Glycosaminoglycans; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012822:Silicon Dioxide; D006820:Hyaluronic Acid