Immunolocalization of CD34 in nasal polyposis. Effect of topical corticosteroids.
Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro with corticosteroid, the findings of the study suggest that in nasal polyp tissue, steroids enhance numbers of CD34(+) progenitors and endothelial cells via indirect mechanisms.
Kim
Y K
YK
Department of Otolaryngology, Inje University, Seoul, Korea.
Uno
M
M
Hamilos
D L
DL
Beck
L
L
Bochner
B
B
Schleimer
R
R
Denburg
J A
JA
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018952:Antigens, CD34 / Q000302:isolation & purification*; D019819:Budesonide / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005938:Glucocorticoids; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D014841:von Willebrand Factor / Q000302:isolation & purification
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D005938:Glucocorticoids; D014841:von Willebrand Factor; D019819:Budesonide