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Laboratory and Animal Investigations |

Increased Levels of Prostaglandin D2 Suggest Macrophage Activation in Patients With Primary Pulmonary Hypertension*

Ivan M. Robbins, MD; Robyn J. Barst, MD; Lewis J. Rubin, MD, FCCP; Sean P. Gaine, MD, FCCP; Patricia V. Price; Jason D. Morrow, MD; Brian W. Christman, MD, FCCP
Author and Funding Information

*From the Center for Lung Research (Drs. Robbins and Christman, and Ms. Price), Department of Medicine, and Division of Clinical Pharmacology (Dr. Morrow), Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN; the Division of Pediatric Cardiology (Dr. Barst), Columbia University Children’s Hospital, New York, NY; the Division of Pulmonary and Critical Care Medicine (Dr. Rubin), UCSD Medical Center, San Diego, CA; and the Division of Pulmonary and Critical Care (Dr. Gaine), Johns Hopkins Hospital, Baltimore, MD.

Correspondence to: Ivan M. Robbins, MD, Vanderbilt University School of Medicine, Room T-1219, MCN, Nashville, TN 37232; e-mail: Ivan.Robbins@mcmail.vanderbilt.edu



Chest. 2001;120(5):1639-1644. doi:10.1378/chest.120.5.1639
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Study objective: TXA2 (thromboxane A2) is a lipid mediator believed to be produced primarily by platelets in normal subjects, although macrophages are capable of synthesis. There is increased production of TXA2 in patients with primary pulmonary hypertension (PPH), which may reflect augmented production by macrophages. The objective of this study was to determine if macrophages are activated in PPH and whether they contribute to the increased production of TXA2.

Study type: Case control.

Setting: University hospital.

Methods: We measured the urinary metabolites of three mediators that predominantly derive from different cell types in vivo: (1) TX-M (platelets and macrophages), a TXA2 metabolite; (2) prostaglandin D2 (PGD2) metabolite (PGD-M); and (3) N-methylhistamine (mast cells), a histamine metabolite, in 12 patients with PPH and 11 normal subjects.

Results: The mean (± SEM) excretion of both TX-M and PGD-M at baseline was increased in PPH patients, compared to normal subjects (460 ± 50 pg/mg creatinine vs 236 ± 16 pg/mg creatinine [p = 0.0006], and 1,390 ± 221 pg/mg creatinine vs 637 ± 65 pg/mg creatinine[ p = 0.005], respectively). N-methylhistamine excretion was not increased compared to normal subjects. There was a poor correlation between excretion of TX-M and PGD-M (r = 0.36) and between excretion of PGD-M and methylhistamine (r = 0.09) in individual patients.

Conclusion: In patients with PPH, increased levels of PGD-M, without increased synthesis of N-methylhistamine, suggest that macrophages are activated. The lack of correlation between urinary metabolite levels of TXA2 and PGD2 implies that macrophages do not contribute substantially to elevated TXA2 production in patients with PPH. They may, however, have a role in the pathogenesis and/or maintenance of PPH, which warrants further investigation.

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