Human alveolar macrophages have 15-lipoxygenase and generate 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid and lipoxins. 1993

B D Levy, and M Romano, and H A Chapman, and J J Reilly, and J Drazen, and C N Serhan
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Eicosanoids derived from lipoxygenase (LO)-catalyzed reactions play important roles in pulmonary inflammation. Here, we examined formation of LO-derived products by human alveolar macrophages (HAM). HAM converted [1-14C]-arachidonic acid to a product carrying 14C-radiolabel that was identified as 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) by physical methods. 15-LO mRNA was demonstrated in HAM by reverse transcription-polymerase chain reaction. Incubation of HAM for 3 d with interleukin 4(IL-4) before exposure to [1-14C]arachidonic acid led to both increased mRNA for 15-LO and a 4-fold increase in 15-HETE formation. In contrast, 5(S)-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid generation was not significantly altered by prior exposure to IL-4. Additionally, lipoxins (LXA4 and LXB4) were detected from endogenous substrate, albeit in lower levels than leukotriene B4 (LTB4), in electrochemical detection/high performance liquid chromatography profiles from HAM incubated in the presence and absence of the chemotactic peptide (FMLP) or the calcium ionophore (A23187). Exposure of HAM to leukotriene A4 (LTA4) resulted in a 2-fold increase in LXA4 and 10-fold increase in LXB4. These results demonstrate the presence of 15-LO mRNA and enzyme activity in HAM and the production of LXA4 and LXB4 by these cells. Along with 5-LO-derived products, the biosynthesis of 15-LO-derived eicosanoids by HAM may also be relevant in modulating inflammatory responses in the lung.

UI MeSH Term Description Entries
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
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006893 Hydroxyeicosatetraenoic Acids Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes. HETE,Acids, Hydroxyeicosatetraenoic
D001093 Arachidonate 15-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES. 15-Lipoxygenase,Arachidonic Acid 15-Lipoxygenase,15 Lipoxygenase,15-Lipoxygenase, Arachidonate,15-Lipoxygenase, Arachidonic Acid,Arachidonate 15 Lipoxygenase,Arachidonic Acid 15 Lipoxygenase
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
D015289 Leukotrienes A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. Leukotriene
D015847 Interleukin-4 A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells. B-Cell Growth Factor-I,B-Cell Stimulatory Factor-1,Binetrakin,IL-4,Mast Cell Growth Factor-2,B Cell Stimulatory Factor-1,B-Cell Growth Factor-1,B-Cell Proliferating Factor,B-Cell Stimulating Factor-1,B-Cell Stimulatory Factor 1,BCGF-1,BSF-1,IL4,MCGF-2,B Cell Growth Factor 1,B Cell Growth Factor I,B Cell Proliferating Factor,B Cell Stimulating Factor 1,B Cell Stimulatory Factor 1,Interleukin 4,Mast Cell Growth Factor 2
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions

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