Increased levels of prostaglandin D(2) suggest macrophage activation in patients with primary pulmonary hypertension.

Robbins IM, Barst RJ, Rubin LJ, Gaine SP, Price PV, Morrow JD, Christman BW
Chest. 2001 120 (5): 1639-44

PMID: 11713147 · DOI:10.1378/chest.120.5.1639

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.

MeSH Terms (16)

Adolescent Adult Case-Control Studies Child Child, Preschool Female Humans Hypertension, Pulmonary Macrophage Activation Macrophages Male Methylhistamines Middle Aged Prostaglandin D2 Prostaglandins D Thromboxane A2

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