Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma

Abstract

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients' clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)-hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6-week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA (r = 0.62; P < 0.005), SCF protein in the NPECs supernatants (r = 0.39; P < 0.05) and with density of mast cells in epithelial layer (r = 0.37; P < 0.05) and stromal layer (r = 0.5; P < 0.01) of nasal polyps. The SCF/beta-actin mRNA ratios were significantly higher in ASA-hypersensitive (AH) asthmatics (median 0.97, range: 0.8-1.5) when compared with ASA-tolerant (AT) patients (median 0.5, range: 0.1-0.7; P < 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/microg DNA, range: 0.4-1.9) when compared with AT patients (median 0.1 pg/microg DNA, range: 0.02-1.2; P < 0.001). In the subpopulation of ASA-sensitive asthmatics the number of polypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue.

Pulmonary IL-17E (IL-25) Production and IL-17RB+ Myeloid Cell-Derived Th2 Cytokine Production Are Dependent upon Stem Cell Factor-Induced Responses during Chronic Allergic Pulmonary Disease

“…Taken together, these studies demonstrate an important mechanistic role for SCF that correlates to observations in human asthma where an increased expression of SCF in the lung and in serum after allergen challenges was observed and correlated to the severity of disease (11)(12)(13)(14). Thus, a complex network of activation may be emerging with SCF as an important initiating cytokine locally in the lung with its ability to activate IL-25 production during allergic responses as well as contribute to the maturation of the IL-17RB ϩ cells in the lung and/or bone in a Th2 immune environment.…”

“…Importantly, SCF and c-kit have been shown to be highly up-regulated in airways of asthmatics (12) as well as in nasal polyps in aspirin-sensitive asthmatics (13), and circulating levels of SCF have been correlated to the severity of asthmatic disease (14). Investigators have also begun examining the role of SCF on eosinophil accumulation and activation.…”

Eosinophil Activation of Fibroblasts from Chronic Allergen-Induced Disease Utilizes Stem Cell Factor for Phenotypic Changes

“…32 Evidence for a role of SCF in human airway disease was supported by studies demonstrating increased SCF expression in nasal polyps of asthmatics and allergic rhinitis patients. 33,34 Additionally, SCF has been implicated as a potential mediator in fibrotic diseases in the kidney and intestine. 34 -37 Recently, the role of SCF has been verified using a chronic Figure 4.…”

Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma

“…20 These original studies were extended by demonstrating that SCF more broadly activates eosinophils for degranulation, mediator release, as well as cytokine and growth factor production, including TGF-b and b-FGF. 21 This general activation pattern indicates the potential role SCF may play in the activation of local fibroblast and structural cell populations for the remodeling of the airway. In addition, the decrease in key inflammatory mediators such as CCL17 when SCF is blocked might reduce the recruitment and activation of Th2 type lymphocytes via CCR4.…”

“…This is supported by data that demonstrated that SCF-stimulated eosinophils had enhanced binding capacity to VCAM-1 and fibronectin, 20 but also appears to initiate a degranulation response and induces pro-fibrotic mediators, leukotrienes and chemokines. 21 Recent data has established increased SCF and c-kit in asthmatic airways 22 and in nasal polyps, 23,24 further supporting a role for SCF/c-kit activation pathways in allergic disease. However, to date no assessment of the role of SCF on chronic allergic disease characterized by severe AHR and peribronchial fibrosis has been performed.…”