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Increased formation of thromboxane in vivo in humans with mastocytosis.

Publication ,  Journal Article
Morrow, JD; Oates, JA; Roberts, LJ; Zackert, WE; Mitchell, TA; Lazarus, G; Guzzo, C
Published in: J Invest Dermatol
July 1999

Clinical manifestations of mastocytosis are mediated, at least in part, by release of the mast cell mediators histamine and prostaglandin D2. It has been previously reported that in addition to prostaglandin D2, mast cells produce other eicosanoids, including thromboxane. Nonetheless, little information exists regarding the formation of other prostanoids in vivo. The most accurate method to examine the systemic production of eicosanoids in vivo is the quantitation of urinary metabolites. We previously developed a highly accurate assay employing mass spectrometry to measure a major urinary metabolite of thromboxane, 11-dehydro-thromboxane B2, in humans. We utilized this assay to quantitate thromboxane production in 17 patients with histologically proven mastocytosis. We report that thromboxane formation was significantly increased (>2 SD above the mean) in at least one urine sample from 65% of patients studied. Of these, 91% of patients with documented systemic involvement had elevated thromboxane generation. In addition, endogenous formation of thromboxane was highly correlated with the urinary excretion of the major urinary metabolite of prostaglandin D2 (r = 0.98) and Ntau-methylhistamine (r = 0.91), suggesting that the cellular source of increased thromboxane in vivo could be the mastocyte. Enhanced thromboxane formation in patients with this disorder is unlikely to be of platelet origin as other markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were not increased in three patients with marked overproduction of thromboxane. Furthermore, the recovery of 11-dehydro-thromboxane B2 excretion in two patients after the administration of aspirin occurred significantly more rapidly than the recovery of platelet thromboxane generation. These studies, therefore, report that thromboxane production is significantly increased in the majority of patients with mastocytosis that we examined and provide the basis to elucidate the role of this eicosanoid in disorders of mast cell activation.

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Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

July 1999

Volume

113

Issue

1

Start / End Page

93 / 97

Location

United States

Related Subject Headings

  • beta-Thromboglobulin
  • Urticaria Pigmentosa
  • Thromboxane B2
  • Prostaglandins D
  • Platelet Factor 4
  • Middle Aged
  • Methylhistamines
  • Male
  • Humans
  • Female
 

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Morrow, J. D., Oates, J. A., Roberts, L. J., Zackert, W. E., Mitchell, T. A., Lazarus, G., & Guzzo, C. (1999). Increased formation of thromboxane in vivo in humans with mastocytosis. J Invest Dermatol, 113(1), 93–97. https://doi.org/10.1046/j.1523-1747.1999.00624.x
Morrow, J. D., J. A. Oates, L. J. Roberts, W. E. Zackert, T. A. Mitchell, G. Lazarus, and C. Guzzo. “Increased formation of thromboxane in vivo in humans with mastocytosis.J Invest Dermatol 113, no. 1 (July 1999): 93–97. https://doi.org/10.1046/j.1523-1747.1999.00624.x.
Morrow JD, Oates JA, Roberts LJ, Zackert WE, Mitchell TA, Lazarus G, et al. Increased formation of thromboxane in vivo in humans with mastocytosis. J Invest Dermatol. 1999 Jul;113(1):93–7.
Morrow, J. D., et al. “Increased formation of thromboxane in vivo in humans with mastocytosis.J Invest Dermatol, vol. 113, no. 1, July 1999, pp. 93–97. Pubmed, doi:10.1046/j.1523-1747.1999.00624.x.
Morrow JD, Oates JA, Roberts LJ, Zackert WE, Mitchell TA, Lazarus G, Guzzo C. Increased formation of thromboxane in vivo in humans with mastocytosis. J Invest Dermatol. 1999 Jul;113(1):93–97.
Journal cover image

Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

July 1999

Volume

113

Issue

1

Start / End Page

93 / 97

Location

United States

Related Subject Headings

  • beta-Thromboglobulin
  • Urticaria Pigmentosa
  • Thromboxane B2
  • Prostaglandins D
  • Platelet Factor 4
  • Middle Aged
  • Methylhistamines
  • Male
  • Humans
  • Female