Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation

• Published in: American journal of physiology. Lung cellular and molecular physiology 2004-03, Vol.286 (3), p.546-L553
• Main Authors: Huang, Weixiong, Wang, Guirong, Phelps, David S, Al-Mondhiry, Hamid, Floros, Joanna
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; Biological Products - pharmacology; Bleomycin - pharmacology; Cell Line; Electrophoresis; Humans; In Vitro Techniques; Insecta; Interleukin-8 - genetics; Mutagenesis; Oxidants, Photochemical - pharmacology; Oxidation-Reduction; Ozone - pharmacology; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00267.2003

Departments of 1 Cellular and Molecular Physiology, 2 Pediatrics, 3 Medicine, and 4 Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 Submitted 31 July 2003 ; accepted in final form 12 November 2003 Surfactant protein A (SP-A) plays a role in innate host defense. Human SP-A is encoded by two functional genes (SP-A1 and SP-A2), and several alleles have been characterized for each gene. We assessed the effect of in vitro expressed human SP-A genetic variants, on TNF- and IL-8 production by THP-1 cells in the presence of bleomycin, either before or after ozone-induced oxidation of the variants. The oligomerization of SP-A variants was also examined. We found 1 ) cytokine levels induced by SP-A2 (1A, 1A 0 ) were significantly higher than those by SP-A1 (6A 2 , 6A 4 ) in the presence of bleomycin. 2 ) In the presence of bleomycin, ozone-induced oxidation significantly decreased the ability of 1A and 1A/6A 4 , but not of 6A 4 , to stimulate TNF- production. 3 ) The synergistic effect of bleomycin/SP-A, either before or after oxidation, can be inhibited to the level of bleomycin alone by surfactant lipids. 4 ) Differences in oligomerization were also observed between SP-A1 and SP-A2. The results indicate that differences among SP-A variants may partly explain the individual variability of pulmonary complications observed during bleomycin chemotherapy and/or in an environment that may promote protein oxidation. inflammation; enzyme-linked immunosorbent assay; oligomerization; ozone Address for reprint requests and other correspondence: J. Floros, Depts. of Cellular and Molecular Physiology, H166, Penn State College of Medicine, 500 Univ. Dr., Hershey, PA 17033 (E-mail: jfloros{at}psu.edu ).