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Am J Physiol Lung Cell Mol Physiol 286: L546-L553, 2004. First published November 14, 2003; doi:10.1152/ajplung.00267.2003
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Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation

Weixiong Huang,1 Guirong Wang,1 David S. Phelps,2 Hamid Al-Mondhiry,3 and Joanna Floros1,2,4

Departments of 1Cellular and Molecular Physiology, 2Pediatrics, 3Medicine, and 4Obstetrics 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-{alpha} 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, 1A0) were significantly higher than those by SP-A1 (6A2, 6A4) in the presence of bleomycin. 2) In the presence of bleomycin, ozone-induced oxidation significantly decreased the ability of 1A and 1A/6A4, but not of 6A4, to stimulate TNF-{alpha} 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).




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