Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma

作者：Hassan Muhannad; Jo Taisuke; Risse Paul Andre; Tolloczko Barbara; Lemiere Catherine; Olivenstein Ronald; Hamid Qutayba; Martin James G^*

来源：Journal of Allergy and Clinical Immunology, 2010, 125(5): 1037-1045.

DOI：10.1016/j.jaci.2010.02.031

• HB-EGF
• PCNA
• Ki 67
• in situ hybridization
• biomarker

Background: The origin of the excess airway smooth muscle in asthma and when in the course of the disease it is acquired are uncertain.
Objectives: We examined the relative sensitivities of 2 markers of proliferation, proliferating cell nuclear antigen (PCNA) and Ki 67, in airway smooth muscle in vivo and in vitro. We then studied whether muscle remodeling is a dynamic process in asthma by quantifying proliferation rate and area. Finally we examined heparin-binding epidermal growth factor as a biomarker of remodeling.
Methods: We obtained bronchoscopic biopsies from subjects with moderate or severe asthma and healthy controls (n = 9/group). For in vitro studies, airway smooth muscle cells were cultured from tracheas of transplant donors. The proliferation rate was quantified from PCNA and Ki 67, co-localized to smooth muscle specific alpha-actin cells in vivo. Muscle area was assessed morphometrically. We examined the expression of heparin-binding epidermal growth factor on tissues by in situ hybridization and by immunohistochemistry and in cells in culture by RT-PCR.
Results: Proliferating cell nuclear antigen and Ki 67 were highly correlated, but PCNA was a significantly more sensitive marker both in vivo and in vitro. Muscle area was 3.4-fold greater and the fraction of PCNA(+) nuclei in muscle was 5-fold greater in severe asthma than in healthy subjects. Heparin-binding epidermal growth factor was upregulated in proliferating muscle cells in culture and in airway smooth muscle in severe asthmatic tissues.
Conclusion: Proliferating cell nuclear antigen is a highly sensitive marker of proliferation and heparin-binding epidermal growth factor is a potential biomarker during active remodeling of ASM in severe asthma. (J Allergy Clin Immunol 2010;125:1037-45.)

• 出版日期2010-5