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.30 (3), p.L546-L553
• Main Authors: WEIXIONG HUANG, GUIRONG WANG, PHELPS, David S, AL-MONDHIRY, Hamid, FLOROS, Joanna
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cells; Cytokines; Fundamental and applied biological sciences. Psychology; Genetics; Oxidation; Ozone; Proteins; Respiratory system; Vertebrates: respiratory system
• ISSN: 1040-0605; 1522-1504

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. [PUBLICATION ABSTRACT]