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
Study type: Case control.
Setting: University hospital.
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.
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.