Effects of inhaled CdO particles on the sphingolipid synthesis of rat lungs.
Surfactant lipids of the alveolar space protect the lung from various environmental stimuli. We investigated the influence of ultrafine (UF) CdO particles inhalation on two key enzymes involved in lung sphingolipid metabolism, serine palmitoyltransferase (SPT), and sphingomyelinase (SMase). Rats inhaled either 0.63 mg UF-CdO/m(3) for 6 h (group 1), or 1.08 mg UF-CdO/m(3) 12 h/day for 10 days (group 2). Two corresponding control groups inhaled filtered clean air. Additional rats intratracheally instilled with lipopolysaccharide (LPS) were used as positive controls. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) of lung tissue showed a significant increase in the level of SPT mRNA (LCB2 subunit) expression in group 2 compared to the corresponding controls (p <.01). Group 1 and LPS were not statistically different from control. No alteration in the mRNA level of SMase was detected in any exposure group. The immunohistochemical analysis showed that SPT (LCB2 subunit) localization was stronger in the alveolar type II cells of group 2 lungs compared to the corresponding controls. These results were correlated with alterations in BALF cellular and biochemical parameters and lung morphology. Since SPT is the key enzyme for de novo sphingolipid synthesis in lung surfactant and SMase is responsible for sphingomyelin catabolism, we can postulate that high-dose UF-CdO exposure for 10 days induces an increase in sphingolipid synthesis in the type II cells of rat lungs that would not be promptly followed by its degradation.
Alessandrini
F
F
Division of Environmental Dermatology and Allergy, GSF Research Center for Environment and Health, Munich, Germany. Franci@gsf.de
Ziesenis
A
A
Takenaka
S
S
Karg
E
E
Heyder
J
J
Ring
J
J
Behrendt
H
H
D000217:Acyltransferases / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019187:Cadmium Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006028:Glycosphingolipids / Q000096:biosynthesis* / Q000502:physiology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000201:enzymology* / Q000473:pathology*; D009929:Organ Size; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects*; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000503:physiopathology; D037661:Pulmonary Surfactant-Associated Proteins / Q000032:analysis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051102:Serine C-Palmitoyltransferase; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
D000336:Aerosols; D019187:Cadmium Compounds; D006028:Glycosphingolipids; D008070:Lipopolysaccharides; D010087:Oxides; D037661:Pulmonary Surfactant-Associated Proteins; C029663:cadmium oxide; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; D012194:RNA-Directed DNA Polymerase; D013108:Sphingomyelin Phosphodiesterase