Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages. 1995

G M VanOtteren, and T J Standiford, and S L Kunkel, and J M Danforth, and R M Strieter
Department of Medicine, University of Michigan Medical School, Ann Arbor, USA.

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008262 Macrophage Activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. Activation, Macrophage,Activations, Macrophage,Macrophage Activations
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004121 Dimethyl Sulfoxide A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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