Department of Pediatrics, Children's Hospital of Philadelphia
Department of Pediatrics
Children's Hospital of Philadelphia
34st Street and Civic Center Blvd
Philadelphia, PA 19104
Phone: (215) 590-3497
Fax: (215) 590-3500
Asthma is characterized by various inflammation-associated effects on the airways, including enhanced airway smooth muscle contractility, airway mucosal edema, and airway smooth muscle cell hyperplasia. Our research is focused on the following:
- evaluating whether various inflammatory mediators modulate airway contractility by altering the expression of receptors coupled to airway smooth muscle cell contraction and relaxation;
- altering the interactions of receptors and G proteins and the subsequent activation of second messenger production;
- modulating the metabolism and binding of second messengers to intracellular receptor sites;
- altering the expression and activity of enzymes associated with contractile protein activation.
Since asthma is characterized by an increase in the mass of airway smooth muscle (ASM) we are also evaluating the role and mechanisms of action of proinflammatory agents and bronchoactive mediators in regulating ASM cell hyperplasia. We have isolated and characterized a cultured rabbit ASM cell line, and demonstrated that various bronchoactive mediators can significantly modulated ASM cell mitogenesis. Our research is directed at evaluating the signal transduction processes coupled to altered ASM cell mitogenesis and other promitogenic events (e.g. protooncogene expression) associated with changes in cell proliferation.
Since conventional tests of lung function cannot be applied to infants, due to their lack of cooperation, another area of our research involves the development of new techniques to measure lung function in infants. Accordingly, we developed a new method to non-invasively measure the static mechanical properties of the respiratory system in infants. We have also recently developed another new method which noninvasively measures the dynamic mechanical properties of the lung, including the dynamic pulmonary compliance and resistance of the airways.
- Grunstein, M.M., C. Springer, S. Godfrey, E. Bar-Yishay, D. Vilozni, and S.C. Inscore. Expiratory volume clamping (EVC): A new method to assess passive respiratory mechanics in infants. J. Appl. Physiol. 62:2107-2114, 1987.
- Tanaka, D.T., and M.M. Grunstein. maturation of neuromodulatory effect of substance P in rabbit airways. J. Clin. Invest. 85:345-350, 1990.
- Grunstein, M.M., C.M. Schramm, S.T. Chang, and N.A. Pawlowski. Role of endothelin-1 in regulating airway contractility. Am. J. Physiol. (Lung Cell Mol. Physiol) 260:75-82, 1991.
- Grunstein, M.M., S.M. Rosenberg, C.M. Schramm, and N.A. Pawlowski. Mechanisms of action of endothelin-1 in maturing rabbit airway smooth muscle. Am. J. Physiol. (Lung Cell Mol. Physiol.) 260:434-443, 1991.
- Rosenberg, S.M., G.T. Berry, J.R. Yandrasitz, and M.M. Grunstein. Maturational regulation of inositol 1, 4, 5-trisphosphate metabolism in rabbit airway smooth muscle. J. Clin. Invest. (In Press), 1991.