OBJECTIVE: To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells called fibrocytes in patients with idiopathic orbital inflammation (IOI). METHODS: Seven patients with IOI were studied. In the 3 patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared with healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all 7 patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40, and collagen 1. Quantitation of CD40-mediated interleukin-6 (IL-6) production was measured using enzyme-linked immunosorbent assay. RESULTS: Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n = 3). Fibrocytes are present in the peripheral blood of IOI patients (n = 7) but are scarce in healthy donors (n = 19). Fibrocytes from IOI patients express substantial levels of CD40, and ligation of CD40 increases IL-6 expression. CONCLUSIONS: Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34(+) fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover, CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy.
OBJECTIVE: To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells called fibrocytes in patients with idiopathic orbital inflammation (IOI). METHODS: Seven patients with IOI were studied. In the 3 patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared with healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all 7 patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40, and collagen 1. Quantitation of CD40-mediated interleukin-6 (IL-6) production was measured using enzyme-linked immunosorbent assay. RESULTS: Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n = 3). Fibrocytes are present in the peripheral blood of IOI patients (n = 7) but are scarce in healthy donors (n = 19). Fibrocytes from IOI patients express substantial levels of CD40, and ligation of CD40 increases IL-6 expression. CONCLUSIONS: Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34(+) fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover, CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy.
Authors: Hayley G Evans; Nicola J Gullick; Stephen Kelly; Costantino Pitzalis; Graham M Lord; Bruce W Kirkham; Leonie S Taams Journal: Proc Natl Acad Sci U S A Date: 2009-03-26 Impact factor: 11.205
Authors: Catherine J Hwang; Nikoo Afifiyan; Daniel Sand; Vibha Naik; Jonathan Said; Stephen J Pollock; Beiling Chen; Richard P Phipps; Robert A Goldberg; Terry J Smith; Raymond S Douglas Journal: Invest Ophthalmol Vis Sci Date: 2008-12-30 Impact factor: 4.799
Authors: Antje Moeller; Sarah E Gilpin; Kjetil Ask; Gerard Cox; Deborah Cook; Jack Gauldie; Peter J Margetts; Laszlo Farkas; Julian Dobranowski; Colm Boylan; Paul M O'Byrne; Robert M Strieter; Martin Kolb Journal: Am J Respir Crit Care Med Date: 2009-01-16 Impact factor: 21.405