The goal of this proposal is the better understanding of upper airways disease processes. Our approach will focus on the involvement of mast cells and basophils, the mediators they release, the plasma enzyme systems (kallikrein-kinin, Hageman Factor and complement), and the subsequent recruitment of other cell types. This will be accomplished with a recently developed in vivo model of allergic rhinitis which involves the recovery of inflammatory mediators after intranasal challenge with antigens to which the subject is sensitive. We have thus far found increased levels of several mast cell products (histamine, PGD2 and a TAMe esterase activity) associated significantly with the physiologic response to the allergen, sneezing. Initial studies will focus on: (1) The quantitaton and characterization of these and other mediators such as kinin, SRS and platelet-activating factor (AGEPC); (2) the use of pharmacologic agonists to characterize both the mechanism of release and the contribution of each mediator; (3) the extension of our preliminary observation which implicates mediator release in the late phase (6 - 12 hours) response to antigen; and (4) confirmation that the response to challenge of the nose with cold, dry air leads to mediator release. Future plans include morphologic examination of the early and late response to antigen to ascertain which cell types are involved and to describe the pathologic processes. We will also examine the response to other potential initiators of upper airways disease. Finally, this versatile model provides a means for comparing in vitro observations with mast cells and basophils with the in vivo response, and this will be vigorously pursued with our present collaborators.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000811-05
Application #
3078187
Study Section
Communicative Disorders Review Committee (CDR)
Project Start
1983-09-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Naclerio, R M; Fisher, C; Civelek, C A et al. (1990) Decrease in xenon clearance during response to cold, dry air: problems of interpretation. Ann Otol Rhinol Laryngol 99:155-9
Hedlin, G; Silber, G; Schieken, L et al. (1989) Attenuation of allergen sensitivity early in the course of ragweed immunotherapy. J Allergy Clin Immunol 84:390-9
Proud, D; Hendley, J O; Gwaltney, J M et al. (1989) Recent studies on the rule of kinins in inflammatory diseases of human airways. Adv Exp Med Biol 247A:117-23
Naclerio, R M; Proud, D; Peters, S P et al. (1986) Inflammatory mediators in nasal secretions during induced rhinitis. Clin Allergy 16:101-10
Baumgarten, C R; Nichols, R C; Naclerio, R M et al. (1986) Concentrations of glandular kallikrein in human nasal secretions increase during experimentally induced allergic rhinitis. J Immunol 137:1323-8
Proud, D; Baumgarten, C R; Naclerio, R M et al. (1986) The role of kinins in human allergic disease. N Engl Reg Allergy Proc 7:213-8
Peters, S P; Naclerio, R M; Freeland, H S et al. (1985) Mast cells and mast cell mediators in models of airway disease. Prog Clin Biol Res 199:153-61
Naclerio, R M; Jenkins, H A; Herzog, J A (1985) Osteoblastoma of the temporal bone presenting as facial paralysis. Int J Pediatr Otorhinolaryngol 8:253-62
Togias, A G; Naclerio, R M; Proud, D et al. (1985) Nasal challenge with cold, dry air results in release of inflammatory mediators. Possible mast cell involvement. J Clin Invest 76:1375-81