Human Airway Smooth Muscle Cells Express the High Affinity Receptor for IgE (FcεRI): A Critical Role of FcεRI in Human Airway Smooth Muscle Cell Function

Abstract

Several reports suggest that activated airway smooth muscle (ASM) cells are capable of generating various proinflammatory mediators, including cytokines and chemokines. However, little is known about the mechanism involved in this process. In this regard, we have examined the expression and the role of the high affinity IgE receptor (FcεRI) by ASM cells. Human ASM cells were found to constitutively express transcripts coding for α, β, and γ subunits of FcεRI. Flow cytometry and Western blot analysis confirmed the expression of FcεRI α-chain protein. Interestingly, FcεRI α-chain immunoreactivity was also demonstrated in smooth muscle within bronchial biopsies of asthmatic subjects. Cross-linking of FcεRI induced mobilization of free calcium in ASM cells, one of the critical signals to trigger smooth muscle contraction. Furthermore, cultured ASM cells released IL-4, IL-13, IL-5, and eotaxin but not IFN-γ, when sensitized with IgE followed by anti-IgE Ab cross-linking. The addition of anti-FcεRI α-chain Abs directed against IgE binding site inhibited this release. Taken together, these results suggest a potential new and important mechanism by which ASM cells may participate in airway inflammation and bronchoconstriction associated with allergic asthma.

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

“…Expression of Fc⑀RII/CD23 mRNA by ASM cells was also detected as previously reported (42). Furthermore, a similar expression pattern was detected in ASM cells obtained from bronchial biopsies of two asthmatic patients (37) and in ASM cells isolated from the central airway of five pathologically uninvolved segments of resected lung specimens (unpublished results). The possibility that a nonspecific expression of Fc⑀RI transcripts by a small number of mast cells, present in our preparations, could have contributed to the Fc⑀RI RNA expression was ruled out since tryptase RNA expression was not detected in our smooth muscle RNA preparations.…”

“…Cross-linking of Fc⑀RI by treating ASM cells with human IgE or anti-Fc⑀RI ␣-chain MAb (15-1) followed by goat anti-mouse IgE or anti-mouse IgG1 induced marked mobilization of intracellular free Ca 2ϩ within 5-10 s; a peak of cytosolic concentrations of Ca 2ϩ (mean peak [Ca 2ϩ ] i ϭ 170 nM) was attained between 10 and 30 s and returned to baseline values thereafter. There was no increase of Ca 2ϩ when irrelevant MAb instead of anti-Fc⑀RI MAb were used, but ASM cells responded well to acetylcholine (mean peak [Ca 2ϩ ] i ϭ 370 nM) (37). Previous reports have demonstrated that contraction of smooth muscle is triggered by an increase in intracellular Ca 2ϩ concentration in response to bronchospastic stimuli (3).…”

“…We found that Fc⑀RI activation on IgE/anti-IgE crosslinking on human ASM and B/TSM cells leads to release of eosinophil mobilizing and chemoattractant factors (IL-5 and eotaxin-1/CCL11) (37). Indeed, preincubation of B/TSM cells with IgE for 4 days followed by passive sensitization for 30 min with IgE to allow saturation of Fc⑀RI, and then cross-linking with anti-human IgE, induced the synthesis and release of eotaxin-1/CCL11 and IL-5 (37).…”

“…The expression pattern was variable according to individual donors (37), which is consistent with previous reports in monocytes (75), dendritic cells (76), eosinophils (34), and neutrophils (35), indicating a level of regulation. Interestingly, Fc⑀RI immunoreactivity was also detected in vivo within ASM cells in bronchial biopsy specimens from six mild atopic asthmatic subjects (37). Because previous reports have described Fc⑀RI-positive cells, i.e., mast cells (12), in the vicinity of the ASM cell layer, we further used an immunofluorescence technique with anti-Fc⑀RI ␣-chain MAb on isolated ASM cells and demonstrated Fc⑀RI ␣-chain protein expression within the isolated ASM cells.…”

“…We have recently demonstrated that human ASM cells express Fc⑀RI (37). The expression of Fc⑀RI ␣, ␤, and ␥ mRNA in cultured bronchial/TSM (B/TSM) cells was detected using RT-PCR analysis.…”