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http://dx.doi.org/10.5352/JLS.2010.20.6.845

Role of Alveolar Macrophages in Productions of Prostaglandin D2 and E2 in the Inflamed Lung  

Joo, Myung-Soo (Division of Applied Medicine, School of Korean Medicine, Pusan National University)
Publication Information
Journal of Life Science / v.20, no.6, 2010 , pp. 845-852 More about this Journal
Abstract
Our previous study showed that lungs infected by Pseudomonas, a gram-negative bacteria, produce prostaglandin $D_2$ ($PGD_2$) and prostaglandin $E_2$ ($PGE_2$), the two major prostanoids generated by cyclooxygenase-2 (COX-2), and that the ratio of $PGD_2$ and $PGE_2$ can affect the outcome of the bacterial lung infection. In this study, we sought to uncover the mechanism that determines the ratio of $PGD_2$ and $PGE_2$ produced in lung inflammation. When treated with lipopolysaccharide (LPS), primary alveolar macrophages, extracted from mouse lung, more $PGE_2$ was produced than $PGD_2$, whereas MH-S, a murine alveolar macrophage cell line, produced more $PGD_2$ than $PGE_2$ in a similar experiment. Western blot analyses showed that the kinetics of COX-2 expression in both cell types is similar and epigenetic silencing of COX-2 expression did not affect expressions of lipocalin-PGD synthase (L-PGDS) and PGE synthase (mPGES-1), major enzymes synthesizing $PGD_2$ and $PGE_2$ in inflammation, respectively, indicating no effect of COX-2 on expressions of the two enzymes. Expressions of L-PGDS and mPGES-1 were also similar in both cell types, suggesting no effect of the two key enzymes in determining the ratio of $PGD_2$ and $PGE_2$ in these cells. A single intraperitoneal injection of LPS to C57BL/6 mice induced COX-2 expression and, similar to alveolar macrophages, produced more $PGE_2$ than $PGD_2$ in the lung. These results suggest that the differential expressions of $PGD_2$ and $PGE_2$ in the lung reflect those in alveolar macrophages and may not be directly determined by the enzymes responsible for $PGD_2$ and $PGE_2$ synthesis.
Keywords
Macrophages; prostaglandin $D_2$; prostaglandin $E_2$; lipopolysaccharide; cyclooxygenase-2; acute lung inflammation;
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1 Tanikawa, N., Y. Ohmiya, H. Ohkubo, K. Hashimoto, K. Kangawa, M. Kojima, S. Ito, and K. Watanabe. 2002. Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem. Biophys. Res. Commun. 291, 884-889.   DOI
2 Joo, M., M. Kwon, R. T. Sadikot, P. J. Kingsley, L. J. Marnett, T. S. Blackwell, R. S. Peebles, Jr., Y. Urade, and J. W. Christman. 2007. Induction and function of lipocalin prostaglandin D synthase in host immunity. J. Immunol. 179, 2565-2575.   DOI
3 Kingsley, P. J., C. A. Rouzer, S. Saleh, and L. J. Marnett. 2005. Simultaneous analysis of prostaglandin glyceryl esters and prostaglandins by electrospray tandem mass spectrometry. Anal. Biochem. 343, 203-211.   DOI
4 Kooguchi, K., S. Hashimoto, A. Kobayashi, Y. Kitamura, I. Kudoh, J. Wiener-Kronish, and T. Sawa. 1998. Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia. Infect. Immun. 66, 3164-3169.
5 Medzhitov, R., P. Preston-Hurlburt, and C. A. Janeway, Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397.   DOI   ScienceOn
6 Muzio, M., G. Natoli, S. Saccani, M. Levrero, and A. Mantovani. 1998. The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J. Exp. Med. 187, 2097-2101.   DOI
7 Richards, M. J., J. R. Edwards, D. H. Culver, and R. P. Gaynes. 1999. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit. Care Med. 27, 887-892.   DOI
8 Rock, F. L., G. Hardiman, J. C. Timans, R. A. Kastelein, and J. F. Bazan. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. U. S. A. 95, 588-593.   DOI
9 Sadikot, R. T., T. S. Blackwell, J. W. Christman, and A. S. Prince. 2005. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 171, 1209-1223.   DOI
10 Broug-Holub, E., G. B. Toews, J. F. van Iwaarden, R. M. Strieter, S. L. Kunkel, R. Paine, III, and T. J. Standiford. 1997. Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival. Infect. Immun. 65, 1139-1146.
11 Devaux, Y., C. Seguin, S. Grosjean, T. N. de, V. Camaeti, A. Burlet, F. Zannad, C. Meistelman, P. M. Mertes, and D. Longrois. 2001. Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase. J. Immunol. 167, 3962-3971.   DOI
12 Guha, M. and N. Mackman. 2001. LPS induction of gene expression in human monocytes. Cell Signal. 13, 85-94.   DOI
13 Dubois, R. N., S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon, L. B. Van De Putte, and P. E. Lipsky. 1998. Cyclooxygenase in biology and disease. FASEB J. 12, 1063-1073.
14 FitzGerald, G. A. 2003. COX-2 and beyond: Approaches to prostaglandin inhibition in human disease. Nat. Rev. Drug Discov. 2, 879-890.   DOI
15 Gilroy, D. W., P. R. Colville-Nash, S. McMaster, D. A. Sawatzky, D. A. Willoughby, and T. Lawrence. 2003. Inducible cyclooxygenase-derived 15-deoxy Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J. 17, 2269-2271.
16 Adamo, R., S. Sokol, G. Soong, M. I. Gomez, and A. Prince. 2004. Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and toll-like receptor 2 as well as toll-like receptor. Am. J. Respir. Cell Mol. Biol. 30, 627-634.   DOI
17 Berg, J. T., S. T. Lee, T. Thepen, C. Y. Lee, and M. F. Tsan. 1993. Depletion of alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate. J. Appl. Physiol. 74, 2812-2819.
18 Hoffken, G. and M. S. Niederman. 2002. Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. Chest 122, 2183-2196.   DOI
19 Beutler, B., X. Du, and A. Poltorak. 2001. Identification of Toll-like receptor 4 (Tlr4) as the sole conduit for LPS signal transduction: genetic and evolutionary studies. J. Endotoxin. Res. 7, 277-280.   DOI
20 Bjorkbacka, H., K. A. Fitzgerald, F. Huet, X. Li, J. A. Gregory, M. A. Lee, C. M. Ordija, N. E. Dowley, D. T. Golenbock, and M. W. Freeman. 2004. The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol. Genomics 19, 319-330.   DOI
21 Soong, G., B. Reddy, S. Sokol, R. Adamo, and A. Prince. 2004. TLR2 is mobilized into an apical lipid raft receptor complex to signal infection in airway epithelial cells. J. Clin. Invest. 113, 1482-1489.   DOI
22 Watanabe, K., K. Kurihara, and T. Suzuki. 1999. Purification and characterization of membrane-bound prostaglandin E synthase from bovine heart. Biochim. Biophys. Acta 1439, 406-414.   DOI   ScienceOn
23 Watanabe, K., K. Kurihara, Y. Tokunaga, and O. Hayaishi. 1997. Two types of microsomal prostaglandin E synthase: glutathione-dependent and -independent prostaglandin E synthases. Biochem. Biophys. Res. Commun. 235, 148-152.   DOI
24 Wine, J. J. 1999. The genesis of cystic fibrosis lung disease. J. Clin. Invest. 103, 309-312.   DOI
25 Zhang, F. X., C. J. Kirschning, R. Mancinelli, X. P. Xu, Y. Jin, E. Faure, A. Mantovani, M. Rothe, M. Muzio, and M. Arditi. 1999. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J. Biol. Chem. 274, 7611-7614.   DOI
26 Sadikot, R. T., H. Zeng, A. C. Azim, M. Joo, S. K. Dey, R. M. Breyer, R. S. Peebles, T. S. Blackwell, and J. W. Christman. 2007. Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2. Eur. J. Immunol. 37, 1001-1009.   DOI
27 Tajima, T., T. Murata, K. Aritake, Y. Urade, H. Hirai, M. Nakamura, H. Ozaki, and M. Hori. 2008. Lipopolysaccharide induces macrophage migration via prostaglandin D(2) and prostaglandin E(2). J. Pharmacol. Exp. Ther. 326, 493-501.   DOI