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HPS1 16-bp duplication (c.1470_1486dup16) induces human mast cell phenotypic changes in vivo and in vitro

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center




  • A Kirshenbaum
  • K O'Brien
  • A Desai
  • G Bandara
  • E Fischer
  • M-Y Jung
  • A Gilfillan
  • W Gahl
  • D Metcalfe


Homozygosity for the HPS1 16-bp duplication(c.1470_1486dup16) results in absence of platelet delta granules/bleeding diathesis, alveolar macrophage accumulation of ceroid lipofuscin/pulmonary fibrosis and granulomatous colitis, and is known as Hermansky-Pudlak Syndrome1(HPS-1). Since macrophages/mast cells share similar precursors, we examined HPS-1 skin, lung and CD34+-derived mast cells for phenotypic changes. Cytopreps and tissue specimens were examined for differences in mast cell morphology and granular ultrastructure. Mast cells cultured from CD34+ cells were examined for histamine, proteases; PGD2,cytokine generation; β-hexosaminidase(βhex) release; CD117/FcεRI/CD64, and the activation markers CD63/CD69/CD203c surface expression; and chemotaxis. Cultured HPS-1 mast cell granules were less dense, and EM of cutaneous HPS-1 mast cells revealed homogeneous granules/electron dense or fine granular structures with few lattices or scrolls. Cutaneous mast cell numbers were similar. HPS1 mast cells contained increased carboxypeptidase, reduced CD117hi, and increased CD63low and CD203c expression. βhex release, PGD2/GM-CSF/TNF-α/TGF-β and IL-6 generation and chemotaxis were similar to controls. We conclude that HPS-1 mast cells are capable of degranulation, cytokine release, and arachidonic acid metabolite generation after FcεRI crosslinking, and normal chemotaxis. However, HPS1 mast cells are morphologically distinct and show upregulation of the activation markers CD63 and CD203c.

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