Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation.
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, 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-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.
Huang
Weixiong
W
Departments of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Wang
Guirong
G
Phelps
David S
DS
Al-Mondhiry
Hamid
H
Floros
Joanna
J
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002460:Cell Line; D004586:Electrophoresis; D006801:Humans; D066298:In Vitro Techniques; D007313:Insecta; D016209:Interleukin-8 / Q000235:genetics*; D016296:Mutagenesis; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010126:Ozone / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D001688:Biological Products; D016209:Interleukin-8; D010083:Oxidants, Photochemical; D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D010126:Ozone; C117342:calfactant