15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects.

BACKGROUND Recent evidence shows that 15(S)-hydroxy-eicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation. OBJECTIVE Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15-lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects. METHODS Levels of 15(S)-HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRINS). Combined immunocytochemistry and PRINS was used to identify the phenotype of cells bearing 15-LO transcripts. RESULTS Levels of both soluble and cell-associated 15(S)-HETE were higher in asthmatic than in control subjects (P <.0001). The percentage of cells expressing 15-LO mRNA was higher in asthmatic than in control subjects (P <.01). On double staining for specific cell-type markers and 15-LO mRNA, macrophages were the major source for 15-LO. CONCLUSION This study shows that the induced sputum technique allows the evaluation of 15-LO activity and that soluble, cell-associated 15(S)-HETE and 15-LO levels are higher in asthmatic than in control subjects. In addition, this study indicates that, in induced sputum, airway macrophages are the major source of 15(S)-HETE in asthma.

[1]  G. Bonsignore,et al.  Interleukin-4 enhances 15-lipoxygenase activity and incorporation of 15(S)-HETE into cellular phospholipids in cultured pulmonary epithelial cells. , 1999, American journal of respiratory cell and molecular biology.

[2]  J. Bousquet,et al.  Increased Levels of Elastase and α1-Antitrypsin in Sputum of Asthmatic Patients , 1998 .

[3]  L. Fabbri,et al.  Integrin upregulation on sputum neutrophils in smokers with chronic airway obstruction. , 1996, American journal of respiratory and critical care medicine.

[4]  J. Bousquet,et al.  5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors , 1996, The Journal of experimental medicine.

[5]  R. Walenga,et al.  Ozone exposure of human tracheal epithelial cells inactivates cyclooxygenase and increases 15-HETE production. , 1995, The American journal of physiology.

[6]  H. Boushey,et al.  Comparison of samples collected by sputum induction and bronchoscopy from asthmatic and healthy subjects. , 1995, American journal of respiratory and critical care medicine.

[7]  M. Matsubara,et al.  Lipoxygenase product formation and cell adhesion during neutrophil-glomerular endothelial cell interaction. , 1995, The American journal of physiology.

[8]  A. A. Spector,et al.  15-HETE: selective incorporation into inositol phospholipids of MDCK cells. , 1994, Kidney international.

[9]  J. Oates,et al.  Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. , 1994, American journal of respiratory and critical care medicine.

[10]  J. Drazen,et al.  Human alveolar macrophages have 15-lipoxygenase and generate 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid and lipoxins. , 1993, The Journal of clinical investigation.

[11]  R. Walenga,et al.  Human tracheal epithelial cells selectively incorporate 15-hydroxyeicosatetraenoic acid into phosphatidylinositol. , 1993, American journal of respiratory cell and molecular biology.

[12]  G. Peluso,et al.  Phenotypic features and secretory pattern of alveolar macrophages in atopic asthmatic patients. , 1993, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[13]  J. Bousquet,et al.  Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi. , 1992, The American review of respiratory disease.

[14]  S. Kelsen,et al.  Eicosanoids PGE2 and PGF2α Enhance the Attachment of Rabbit Tracheal Epithelial Cells to a Collagen Substrate , 1992 .

[15]  J. Bousquet,et al.  Functional assessment of viability of epithelial cells. Comparison of viability and mediator release in healthy subjects and asthmatics. , 1992, Chest.

[16]  H. Kuhn,et al.  Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  L. Bolund,et al.  Fast one-step procedure for the detection of nucleic acids in situ by primer-induced sequence-specific labeling with fluorescein-12-dUTP. , 1992, Cytogenetics and cell genetics.

[18]  C. Chavis,et al.  Formation of lipoxins and leukotrienes by human alveolar macrophages incubated with 15(S)-HETE: a model for cellular cooperation between macrophages and airway epithelial cells. , 1992, Eicosanoids.

[19]  J. Oates,et al.  Substitution of 15-hydroxyeicosatetraenoic acid in the phosphoinositide signaling pathway. , 1991, The Journal of biological chemistry.

[20]  D. Steinberg,et al.  Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. , 1991, The Journal of clinical investigation.

[21]  C. Chavis,et al.  Sulfidopeptide leukotrienes contribute to human alveolar macrophage activation in asthma. , 1991, Prostaglandins, leukotrienes, and essential fatty acids.

[22]  M. Hamberg,et al.  15(S)-hydroxyeicosatetraenoic acid is the major arachidonic acid metabolite in human bronchi: association with airway epithelium. , 1990, Archives of biochemistry and biophysics.

[23]  M. Brezinski,et al.  Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: agonist-induced deacylation and transformation of stored hydroxyeicosanoids. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  S. Holgate,et al.  Effect of 15-(s)-hydroxyeicosatetraenoic acid on allergen-induced asthmatic responses. , 1990, The American review of respiratory disease.

[25]  M. Chan-yeung,et al.  Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. , 1989, American journal of respiratory cell and molecular biology.

[26]  J. Rankin,et al.  The contribution of alveolar macrophages to hyperreactive airway disease. , 1989, The Journal of allergy and clinical immunology.

[27]  M. Peters-Golden,et al.  Arachidonic acid metabolism in cultured alveolar macrophages from normal, atopic, and asthmatic subjects. , 1988, The American review of respiratory disease.

[28]  J. Vanderhoek,et al.  Role of the 15‐Lipoxygenase in the Immune System a , 1988, Annals of the New York Academy of Sciences.

[29]  R. Fuller,et al.  Human alveolar macrophage activation: inhibition by forskolin but not beta-adrenoceptor stimulation or phosphodiesterase inhibition. , 1988, Pulmonary pharmacology.

[30]  C. Chavis,et al.  Arachidonic acid metabolism in alveolar macrophages. A comparison of cells from healthy subjects, allergic asthmatics, and chronic bronchitis patients. , 1987, Prostaglandins.

[31]  J. Murray,et al.  Release of prostaglandin D2 into human airways during acute antigen challenge. , 1986, The New England journal of medicine.

[32]  C. Chavis,et al.  Effect of nedocromil sodium on TXB2, LTB4 and LTD4 synthesis by alveolar macrophages from asthmatic patients. , 1986, European journal of respiratory diseases. Supplement.

[33]  E. Goetzl,et al.  Predominant generation of 15-lipoxygenase metabolites of arachidonic acid by epithelial cells from human trachea. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[34]  F. Sun,et al.  15-Hydroxyeicosatetraenoic acid is a potent inflammatory mediator and agonist of canine tracheal mucus secretion. , 1985, The American review of respiratory disease.

[35]  I. Olsson,et al.  Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein , 1984, Nature.

[36]  H Stein,et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[37]  J. Shelhamer,et al.  Human airway monohydroxyeicosatetraenoic acid generation and mucus release. , 1983, The Journal of clinical investigation.

[38]  A. Capron,et al.  Involvement of immunoglobulin E in the secretory processes of alveolar macrophages from asthmatic patients. , 1983, The Journal of clinical investigation.

[39]  P. Godard,et al.  Functional assessment of alveolar macrophages: comparison of cells from asthmatics and normal subjects. , 1982, The Journal of allergy and clinical immunology.

[40]  J. Oates,et al.  Arachidonic acid 15-lipoxygenase products from human eosinophils. , 1982, The Journal of biological chemistry.

[41]  M. Hamberg,et al.  Identification of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) as a major metabolite of arachidonic acid in human lung. , 1980, Acta physiologica Scandinavica.