The program has the following goals and objectives. 1. To maintain a colony of 3 groups of rhesus monkeys including normal animals, animals with IgE mediated cutaneous and airway reactivity to ascaris antigen or animals with IgE positive skin reactivity but negative airway reactivity. Because the antigen airway reactors have hyperreative airways this group of allergic rhesus monkeys may closely simulate human IgE mediated asthma. 2. To establish quantitative dose-response reactions to antigen and carbocholine in antigen reactive monkeys and carbocholine reactivity in normal monkeys. The carbocholine reactivity will be an index of the degree of hyperreactivity of the airway. 3. To determine qualitative and quantitative responses to potentially important agonists of airway reactions in selected asthmatics and controls monkeys. These agonists will include leukotriene D4 (LTD4), platelet activating factor (PAF) and histamine releasing agent (HRA) in selected asthmatic and control monkeys for evaluation of qualitative and quantitative individual animal responses. 4. To study receptor antagonists against LTD4 and PAF as inhibiting agents for these agonists and for antigen induced asthma. A lipoxygenase inhibitor will be studied to determine if antigen induced asthma is diminished by pretreating with this agent. The airway response to HRA will be evaluated by using antagonists against H, LTD4 and PAF. 5. To define the pattern of bioactive mediators released into bronchoalveolar lavage (BAL) fluid after antigen challenge and challenge with these mediators. 6. To develop a monkey model of toluene diisocyanate (TDI) asthma based on our human clinical experience in man and our experience with a canine model of TDI asthma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI020060-05
Application #
3129555
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1983-09-01
Project End
1992-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Patterson, R; Harris, K E (1993) Substance P and IgE-mediated allergy. I. Transient increase in airway responsiveness to allergen in primates. Allergy Proc 14:45-51
Lowenthal, M; Patterson, R; Harris, K E (1993) Passive transfer of IgE-mediated cutaneous reactivity in heterologous species. Ann Allergy 71:481-4
Patterson, R; Harris, K E (1993) Substance P and IgE-mediated allergy. II. Reduction of rhesus IgE antibody after aerosol exposure to substance P and allergen. Allergy Proc 14:53-9
Patterson, R; Harris, K E (1992) IgE-mediated rhesus monkey asthma: natural history and individual animal variation. Int Arch Allergy Immunol 97:154-9
Patterson, R; Harris, K E (1990) Rhesus monkey airway responses to substance P. Int Arch Allergy Appl Immunol 91:374-9
Patterson, R; Harris, K E; Bernstein, P R et al. (1989) Effects of combined receptor antagonists of leukotriene D4 (LTD4) and platelet-activating factor (PAF) on rhesus airway responses to LTD4, PAF and antigen. Int Arch Allergy Appl Immunol 88:462-70
Patterson, R; Harris, K E; Krell, R D (1988) Effect of a leukotriene D4 (LTD4) antagonist on LTD4 and ascaris antigen-induced airway responses in rhesus monkeys. Int Arch Allergy Appl Immunol 86:440-5
Patterson, R; Harris, K E; Handley, D A et al. (1987) Evaluation of the effect of a platelet activating factor antagonist on platelet activating factor and Ascaris antigen-induced airway responses in rhesus monkeys. J Lab Clin Med 110:606-11
Patterson, R; Harris, K E; Bernstein, P R et al. (1986) Aerosolized leukotriene D4 converts monkeys that are negative aerosolized ascaris responders to positive airway responders. Life Sci 38:1179-84
Patterson, R; Harris, K E; Lee, M L et al. (1986) Inhibition of rhesus monkey airway and cutaneous responses to platelet-activating factor (PAF) (AGEPC) with the anti-PAF agent SRI 63-072. Int Arch Allergy Appl Immunol 81:265-8

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