Purchase this article with an account.
M.S. Razzaque, Y.J. Daoud, K.A. Rashid, C.S. Foster, A.R. Ahmed; Molecular mechanism that determines the macrophage population in ocular cicatricial pemphigoid . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1484.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Monocytes and macrophages are important participants in various immunoinflammatory diseases including ocular cicatricial pemphigoid (OCP). The molecular mechanism that determines macrophage population in OCP is not yet clear. We have recently demonstrated that macrophage colony–stimulating factor (m–CSF) might play a role in the regulation of conjunctival macrophage population in OCP (Razzaque et. al., IOVS 43:2977–83, 2002). Similar to m–CSF, macrophage migration inhibitory factor (MIF) plays important role in determining the macrophage population in various immunoinflammatory diseases, by inhibiting the migration of macrophages from the affected sites and organs. In this study, we have examined the role of MIF in the pathogenesis of OCP. Methods: The expression of MIF in conjunctival tissues of patients with OCP (n=10), and normal subjects (n=5), were studied by quantitative real–time PCR and immunohistochemistry. The ability of conjunctival fibroblasts to produce MIF was measured, by using real–time PCR and ELISA. In addition, the effects of IL–1, IL–4, IL–13, TNF–alpha and TGF–beta1 on the expression of MIF by conjunctival fibroblasts were also studied. To determine the relationship between the expression of MIF and the conjunctival accumulation of macrophages, a correlation study was performed. Results: An increased expression of MIF was detected in conjunctival tissues of OCP patients, both at the mRNA (by real–time PCR) and protein level (by immunohistochemistry), compared to normal controls. Similar increase in the expression of MIF was detected in fibroblasts isolated from conjunctiva of OCP patients, compared to control fibroblasts. A statistically significant increase (p<0.001) in the level of MIF was also detected in supernatant collected from conjunctival fibroblasts of OCP patients (188±5.4), compared to control fibroblasts (9.4±7.6), by ELISA. Moreover, IL–1, IL–4, IL–13, TNF–alpha and TGF–beta1, known factors involved in the pathogenesis of OCP, were found to induce the expression of MIF by conjunctival fibroblasts. A statistically significant correlation (p<0.001, r2=0.4465) was observed between the expression of MIF and accumulation of CD–68–positive macrophages in conjunctiva of patients with OCP. Conclusions:Increased conjunctival expression of MIF might partly regulate macrophages population in patients with OCP, and thereby could enhance immunoinflammatory responses in these patients.
This PDF is available to Subscribers Only