Studies comparing pulmonary responses to crystalline silica (SiO2) and titanium dioxide (0.3 μm diameter, TiO2-F) demonstrated a positive correlation between alveolar macrophage (AM) release of interleukin-1 (IL-1), tumor necrosis factor (TNF) and fibronectin and, pulmonary granuloma formation, inflammation and fibrosis, respectively. AM IL-1 release was associated with the development of pulmonary granulomas after SiO2 exposure. AM release of TNF positively correlated with the degree of neutrophil recruitment after SiO2 or TiO2-F exposure. A persistent increase in AM fibronectin release consistently correlated with the development of pulmonary fibrosis after SiO2 or TiO2-F exposure. Studies comparing pulmonary responses to ultrafine TiO2 (TiO2-D; particle diameter, 0.02 μm) with TiO2-F demonstrate that ultrafine particles have a relatively greater toxicity on a mass/lung basis. Exposure to TiO2-D resulted in a persistent increase in AM TNF and fibronectin release which was associated with neutrophil recruitment and fibrosis, respectively. TiO2-D did not stimulate AM IL-1 release and this was consistent with the absence of a granulomatous response to TiO2-D. In light of the known bioactivities of IL-1, TNF and fibronectin, these correlative findings suggest that these mediators play significant roles in pulmonary responses to mineral dust exposure and may serve as potential early biomarkers of pulmonary toxicity.
AdamsonIYR (1990). Cellular responses and translocation of particles following deposition in the lung.J. Amer. Med.3: s31–s42.
2.
AdamsonIYR and BowdenDH (1981). Dose-re-sponse of the lung pulmonary macrophagic system to various particulates and its relationship to transepithelial passage of free particles.Exp. Lung Res.2: 165–175.
3.
AdamsonIYR, LetourneauHL, and BowdenDH (1989). Enhanced macrophage-fibroblast interactions in the pulmonary interstitium increases fibrosis after silica injection to monocyte-depleted mice.Am. J. Pathol.134:411–418.
4.
BevilacquaMP, StengelinS, GimbroneMA, and SeedB (1989) Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory protein and lectins.Science243: 1160–1164.
5.
BittermanPB, RennardSI, AdelbergS, and CrystalR (1983). Role of fibronectin as a growth factor for fibroblasts.J Cell. Biol.97: 1925–1932.
6.
BittermanPB, WewersMD, RennardSI, AdelbergS, and CrystalRG (1986). Modulation of alveolar macrophage-driven fibroblast proliferation by alternative macrophage mediators.J. Clin. Invest.77: 700–708.
7.
BowdenD and AdamsonIYR (1982). Alveolar macrophage response to carbon in monocyte depleted mice.Am. Rev. Resp. Dis.126: 708–711.
8.
ClarkRA, DellaPelleP, ManseauE, LaniganJM, DvorakHF, and ColvinRB (1982). Blood vessel fibronectin increases in conjunction with endothelial cell proliferation and capillary ingrowth during wound healing.J. Invest. Derm.9: 269–280.
9.
DriscollKE, LindenschmidtRC, MaurerJK, HigginsJM, and RidderG (1990). Pulmonary response to silica or titanium dioxide: Inflammatory cells, alveolar macrophage-derived cytokines, and histopathology.Am. J. Resp. Cell Mol. Biol.2: 381–390.
10.
DriscollKE, MaurerJK, LindenschmidtRC, RombergerD, RennardSI, and CrosbyL (1990). Respiratory tract responses to dust: Relationship between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis.Toxicol. Appl. Pharmacol.106: 88–101.
11.
DriscollKE, HigginsJ, RombergerD, RennardSI, and CrosbyL (1990). Alveolar macrophage tumor necrosis factor and fibronectin release in asbestos or cadmium chloride-induced pulmonary injury and fibrosis.Am. Rev. Resp. Dis.141: A416.
12.
DriscollKE, MaurerJK, and JordanJ (1991). Activation of alveolar macrophage secretory activity after exposure to ultrafine aluminum oxide dust particles.Am. Rev. Resp. Dis.143: A698.
13.
DunnCJ and FlemingWE (1984). Increased adhesion of polymorphonuclear leukocytes to vacular endothelium by specific interaction by endogenous (interleukin-1) and exogenous (lipopolysaccharide) substances with endothelial cells in vitro.Eur. J. Rheum. Inflam.7: 80–86.
14.
DunnCJ, HardeeMM, GibbonsAJ, StaiteND, and RichardKA (1988). Local pathological responses to slow-release recombinant interleukin-1, interleukin-2 and g-interferon in the mouse and their relevance to chronic inflammatory disease.Clin. Sci.76:261–263.
15.
FerinJ and FeldsteinML (1978). Pulmonary clearance and hilar lymph node content in rats after particle exposure.Environ. Res.16: 342–352.
16.
FerinJ., OberdorsterG, SoderholmSC, and GeleinR (1991) Pulmonary tissue access of ultrafine particles.J. Aerosol Med.4: 57–68.
17.
HunninghakeGW (1984). Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis.Am. Rev. Resp. Dis.129: 569–572.
18.
KasaharaK., KobayashiK, ShikamaY, SoezimaK, IdeH, and TakahashiT (1989). Direct evidence for granuloma-inducing role of interleukin-1.Am. J. Pathol.130: 629–638.
19.
KlempnerMS, DinarelloCA, and GallinJI (1978). Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.J. Clin. Invest.61: 1330–1336.
20.
KlebanoffSJ, VadasMA, HarlanJM, SparksLH, GambleJR, AgostiJM, and WaltersdorphAM (1986). Stimulation of neutrophils by tumor necrosis factor.J Immunol136: 4220–4225.
21.
LeJ and VilcekJ (1987). Tumor necrosis factor and interleukin-1: Cytokines with multiple overlapping biological activities.Lab. Invest.56: 234–248.
22.
MacarakEJ and HowardPS (1983). Adhesion of endothelial cells to extracellular matrix proteins.J. Cell Physiol.116: 76–86.
23.
OberdorsterG., FerinJ, GeleinR, SoderholmS, CoxC, BaggsR, and FinkelsteinJ (1991). Inhaled ultrafine particles: Evidence of their increased pulmonary toxicity.Am. Rev. Resp. Dis.143: A700.
24.
PostlethwaiteAE, Kesky-OjaJ, BalianG, and KangAH (1980). Induction of fibroblast Chemotaxis by fibronectin: Localization of the chemotactic region to an 140,000 molecular weight non-gelatin binding fragment.J. Exp. Med.153: 494–499.
25.
RennardSI, HunninghakeGW, BittermanPB, and CrystalR (1981). Production of fibronectin by the human alveolar macrophage: Mechanism for the recruitment of fibroblasts to sites of tissue injury and interstital lung disease.Proc. Natl. Acd. Sci. USA78: 7147–7151.
26.
RomWN, BittermanPB, RennardSI, CantinA, and CrystalRG (1987). Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts.Am. Rev. Resp. Dis.136: 1429–1434.
27.
RomWH (1991). Relationship of inflammatory cell cytokines to disease severity in individuals with occupational inorganic dust exposure.Am. J. Ind. Med.19: 15–27.
28.
StreiterRM, KunkelSL, ShowellHJ, RemickDG, PhanSH, WardPA, and MarkRM (1989). Endothelial cell gene expression of a neutrophil chemotactic factor by TNFΑ, LPS, and IL-1β.Science243: 1467–1469.
29.
WarrenJS, KunkelSL, CunninghamTW, JohnsonKJ, and WardPA (1988). Macrophage-derived cytokines amplify immune complex-triggered O2- responses by rat alveolar macrophages.Am. J. Pathol.130: 489–495.
