Increased levels of prostaglandin D(2) suggest macrophage activation in patients with primary pulmonary hypertension - PubMed (original) (raw)
Increased levels of prostaglandin D(2) suggest macrophage activation in patients with primary pulmonary hypertension
I M Robbins et al. Chest. 2001 Nov.
Abstract
Study objective: TXA(2) (thromboxane A(2)) 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 TXA(2) 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 TXA(2).
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 TXA(2) metabolite; (2) prostaglandin D(2) (PGD(2)) 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 TXA(2) and PGD(2) implies that macrophages do not contribute substantially to elevated TXA(2) production in patients with PPH. They may, however, have a role in the pathogenesis and/or maintenance of PPH, which warrants further investigation.
Similar articles
- Improved diagnosis of mastocytosis by measurement of the major urinary metabolite of prostaglandin D2.
Morrow JD, Guzzo C, Lazarus G, Oates JA, Roberts LJ 2nd. Morrow JD, et al. J Invest Dermatol. 1995 Jun;104(6):937-40. doi: 10.1111/1523-1747.ep12606209. J Invest Dermatol. 1995. PMID: 7769262 - An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension.
Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, Loyd JE. Christman BW, et al. N Engl J Med. 1992 Jul 9;327(2):70-5. doi: 10.1056/NEJM199207093270202. N Engl J Med. 1992. PMID: 1603138 - Lipid mediator dysregulation in primary pulmonary hypertension.
Christman BW. Christman BW. Chest. 1998 Sep;114(3 Suppl):205S-207S. doi: 10.1378/chest.114.3_supplement.205s. Chest. 1998. PMID: 9741570 Review. - Oxidant stress but not thromboxane decreases with epoprostenol therapy.
Robbins IM, Morrow JD, Christman BW. Robbins IM, et al. Free Radic Biol Med. 2005 Mar 1;38(5):568-74. doi: 10.1016/j.freeradbiomed.2004.11.033. Free Radic Biol Med. 2005. PMID: 15683712 - On the role of PGD2 metabolites as markers of mast cell activation in asthma.
O'Sullivan S. O'Sullivan S. Acta Physiol Scand Suppl. 1999 Apr;644:1-74. Acta Physiol Scand Suppl. 1999. PMID: 10352758 Review.
Cited by
- Predictors of osteoclast activity in patients with sickle cell disease.
Nouraie M, Cheng K, Niu X, Moore-King E, Fadojutimi-Akinsi MF, Minniti CP, Sable C, Rana S, Dham N, Campbell A, Ensing G, Kato GJ, Gladwin MT, Castro OL, Gordeuk VR. Nouraie M, et al. Haematologica. 2011 Aug;96(8):1092-8. doi: 10.3324/haematol.2011.042499. Epub 2011 May 5. Haematologica. 2011. PMID: 21546502 Free PMC article. - Pathogenic Mechanisms of Pulmonary Arterial Hypertension: Homeostasis Imbalance of Endothelium-Derived Relaxing and Contracting Factors.
Zhu J, Yang L, Jia Y, Balistrieri A, Fraidenburg DR, Wang J, Tang H, Yuan JX. Zhu J, et al. JACC Asia. 2022 Dec 15;2(7):787-802. doi: 10.1016/j.jacasi.2022.09.010. eCollection 2022 Dec. JACC Asia. 2022. PMID: 36713766 Free PMC article. Review. - A case of pulmonary arterial hypertension associated with adult hemophagocytic lymphohistiocytosis.
Koifman J, Granton J, Thenganatt J. Koifman J, et al. Pulm Circ. 2016 Dec;6(4):614-615. doi: 10.1086/688490. Pulm Circ. 2016. PMID: 28090306 Free PMC article. - Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling.
He Y, Zuo C, Jia D, Bai P, Kong D, Chen D, Liu G, Li J, Wang Y, Chen G, Yan S, Xiao B, Zhang J, Piao L, Li Y, Deng Y, Li B, Roux PP, Andreasson KI, Breyer RM, Su Y, Wang J, Lyu A, Shen Y, Yu Y. He Y, et al. Am J Respir Crit Care Med. 2020 May 15;201(10):1263-1276. doi: 10.1164/rccm.201911-2137OC. Am J Respir Crit Care Med. 2020. PMID: 31917615 Free PMC article. - A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension.
Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, Jiang W, Vangala N, Landsberg JW, Wang JY, Thistlethwaite PA, Channick RN, Robbins IM, Loyd JE, Ghofrani HA, Grimminger F, Schermuly RT, Cahalan MD, Rubin LJ, Yuan JX. Yu Y, et al. Circulation. 2009 May 5;119(17):2313-22. doi: 10.1161/CIRCULATIONAHA.108.782458. Epub 2009 Apr 20. Circulation. 2009. PMID: 19380626 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- CA68485/CA/NCI NIH HHS/United States
- CA77839/CA/NCI NIH HHS/United States
- DK26657/DK/NIDDK NIH HHS/United States
- DK48831/DK/NIDDK NIH HHS/United States
- GM15431/GM/NIGMS NIH HHS/United States
- GM42056/GM/NIGMS NIH HHS/United States
- HL55198/HL/NHLBI NIH HHS/United States
- RR-00095/RR/NCRR NIH HHS/United States
- RR-00645/RR/NCRR NIH HHS/United States
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous