RESUMO
BACKGROUND: Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. METHODS: Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. RESULTS: The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 +/- 4.2% (IL-4), 15.6 +/- 2.7% (GM-CSF) and 32.9 +/- 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Ralpha and a low level expression of IL-2Rgammac in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rgammac. CONCLUSION: CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC.
RESUMO
BACKGROUND: Both hyper-IgE syndrome and food allergies can result in the early onset of skin rash, eosinophilia, and markedly elevated serum IgE. Occasionally, it can be difficult to distinguish the 2 disorders. Most patients with hyper-IgE syndrome do not have food allergy. OBJECTIVE: To describe a child with cow's milk allergy associated with hyper-IgE syndrome manifesting as failure to thrive (FTT). METHODS: Epicutaneous skin prick test to cow's milk, CAP radioallergosorbent test, atopy patch tests, and double-blind, placebo-controlled milk challenge (DBPCMC) were performed. RESULTS: During initial presentation at 3 weeks of age, the circulating eosinophil count increased from 13,800/mm3 to 44,254/mm3 within 2 weeks while taking cephalexin. Despite treatment, he had worsening rash and FTT at 10 weeks of age with an IgE level of 8,454 U/mL. After changing from an infant milk formula with whey protein to an amino acid-based formula in combination with oral antibiotic treatment, his rash and growth velocity improved markedly within 2 months. IgE decreased to 2,747 U/mL. He remained clinically well for 12 months. He subsequently developed additional food and inhalant allergies with an increase in IgE to 12,150 U/mL. Cow's milk allergy was confirmed by epicutaneous skin prick test, atopy patch test, and DBPCMC. CONCLUSIONS: Traditional prophylactic antistaphylococcal antibiotics, in combination with Neocate formula, were effective in treating the early skin manifestations of hyper-IgE syndrome and FTT in this infant. Cow's milk protein allergy should be considered in patients with hyper-IgE syndrome and FTT.
