Dysfunction of releasing adrenaline in asthma by nerve growth factor.
In early embryo period, adrenal medulla development is parallel with adrenergic nerves. For this reason, adrenal medullary cells may be provided with potential ability of transdifferentiation toward nerve cells. In vitro, it was well testified that if adrenal medullary cells are treated with nerve growth factor, then the cells will be transdifferentiated toward sympathetic neurons characterized by morphous, biochemistry and physiological functions. As a result, adrenal medullary cells after being transdifferentiated may be impaired in the functions of endocrine secretion, and the composition and level of adrenal medullary hormone are changed. The above mentioned may be regarded as the reflection of cellular redundancy, besides the transdifferentiation, multiple organelle copies, cellular plasticity and so on are all reflections of cellular redundancy. According to cellular redundancy, in addition to their regular and specific functions, some cells(types) are of other additional functions which will be activated in special state such as diseases, external interference and so on. The theory of cellular redundancy is seemed to unpuzzle the dysfunction of releasing adrenaline in asthma. Compared with the normal control group, the study showed that the levels of adrenaline in the asthmatic patients were not increased when patients encountered the strong stimuli. Subsequently, overexpression of nerve growth factor was also detected in asthmatic patients and animals. However, accompanied with alleviation of airway inflammation, these phenomena were changed when asthmatic models were treated with antibody of nerve growth factor. What makes these phenomena linked? The existence of functional redundancy of medullary cells may be the most important factor. This hypothesis suggests that overexpression of nerve growth factor activate functional redundancy of adrenal medullary cells, which makes these cells transdifferentiated toward sympathetic neurons. The transdifferentiation (tendency) may impair the functions of endocrine secretion of adrenal medullary cells. As a result, adrenal medulla cannot release enough adrenaline to relieve bronchoconstriction in asthmatic attack.
Feng
Jun Tao
JT
Department of Respiratory Medicine, XiangYa Hospital, Central South University, No. 141 XiangYa Road, Changsha, Hunan 410008, China.
Hu
Cheng Ping
CP
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D019317:Evidence-Based Medicine; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism*
D013373:Substance P; D020932:Nerve Growth Factor; D004837:Epinephrine