Pulmonary response to inhaled silica or titanium dioxide.
The pulmonary response to mineral dust inhalation was investigated by characterizing markers of lung injury and inflammation, macrophage activation, dust clearance, and histopathology. Rats were exposed (6 hr/day x 5 days) to air or 50 mg/m3 crystalline silica (SiO2) or titanium dioxide (TiO2). At 7, 14, 28, and 63 days after exposure, bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, and N-acetylglucosaminidase, as well as cell number, type, and viability. Alveolar macrophages (AM) obtained in BALF were cultured with or without LPS and release of interleukin-1 (IL-1) and fibronectin was determined. Histopathology was conducted at 28 and 63 days. The exposure protocol resulted in 1.8-1.9 mg of mineral dust being deposited in the pulmonary region. Clearance of SiO2 was significantly less than TiO2. SiO2 increased BALF neutrophils (Days 14, 28, and 63), total protein (Days 28 and 63), and LDH and lymphocytes (Day 63). SiO2 increased AM-derived fibronectin release (Day 63) and LPS-induced IL-1 release (all time points), but not spontaneous release of IL-1. TiO2 did not change BALF biochemical or cellular parameters or AM secretory activity. Histopathology revealed minimal interstitial inflammation with SiO2 and no significant response in control or TiO2 rats. These results demonstrate the pulmonary response to inhaled SiO2 can be differentiated from the relatively innocuous TiO2 by changes in BALF markers of injury and inflammation further supporting the use of BALF analysis to make relative assessments of pulmonary toxicity. The stimulation of macrophage fibronectin release by the fibrogenic dust SiO2 and not TiO2 is consistent with a role for this glycoprotein in lung injury and repair. Last, the early and persistent effect of SiO2 on LPS-induced AM IL-1 release indicates this response may represent a sensitive early marker of dust-induced changes in the AM population.
Driscoll
K E
KE
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
Lindenschmidt
R C
RC
Maurer
J K
JK
Perkins
L
L
Perkins
M
M
Higgins
J
J
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004333:Drug Administration Routes; D004391:Dust / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000009:adverse effects*; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects*; D014132:Trachea
D004391:Dust; D008903:Minerals; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium