The inflammatory process is essential for host defense against infection and for survival. Two of the initial events of inflammation, increased vascular permeability and infiltration of phagocytic cells, are mediated by C3a and C5a, the samll cleavage fragments of the third (C3) and fifth (C5) components of complement (C). The experiments presented in this application will investigate the regulation of synthesis of the C3 and C5, and other acute phase proteins (APP), during inflammation. The first series of experiments will determine the regulation of synthesis of C3 and C5 in vitro by human macrophages (peripheral blood monocyte-derived macrophages). The role of agents that could be at active sites of inflammation in stimulating these cells to produce increased amounts of C3 and C5 will be determined. The stimuli to be used will include phagocytic particles, lipopolysaccharide and phospholipase A2. We will then determine if the C3 and C5 produced by the human macrophages are precursors for the phlogistic fragments, C3a and C5a, the activity of which will be measured using standard biologic assays. The second set of experiments will investigate the role of surfaces comprised of proteins present in inflammatory sites in supporting production of C by human macrophages. The proteins used will be fibrinogen, collagen, gelatin (denatured collagen) and fibronectin. Finally, in vivo synthesis rates of C3 and C5 (as well as ceruloplasmin, another APP) by liver will be measured at various times after induction of turpentine pleurisy in rabbits. We will then attempt to define the blood-borne, soluble mediator(s) responsible for the changes in synthetic rates of the APP using an in vitro system with rabbit liver cells. We will then determine if synthesis of each APP is controlled by a separate mediator, or if a single mediator controls synthesis of all the APP, and if a single APP can be controlled by more than one mediator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07AI000543-04
Application #
3076698
Study Section
Allergy and Immunology Research Committee (AIRC)
Project Start
1983-09-01
Project End
1987-06-30
Budget Start
1986-09-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206
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Strunk, R C (1989) Management of systemic steroid therapy for asthma: an art form not likely to be replaced by computer decision making. J Asthma 26:157-8
Strunk, R C; Fukuhara, J T; LaBrecque, J F et al. (1989) Outcome of long-term hospitalization for asthma in children. J Allergy Clin Immunol 83:17-25
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Strunk, R C; Rubin, D; Kelly, L et al. (1988) Determination of fitness in children with asthma. Use of standardized tests for functional endurance, body fat composition, flexibility, and abdominal strength. Am J Dis Child 142:940-4
Adinoff, A D; Schlosberg, R T; Strunk, R C (1988) Methacholine inhalation challenge in young children: results of testing and follow-up. Ann Allergy 61:282-6
Brenner, M; Berkowitz, R; Marshall, N et al. (1988) Need for theophylline in severe steroid-requiring asthmatics. Clin Allergy 18:143-50
Katz, Y; Cole, F S; Strunk, R C (1988) Synergism between gamma interferon and lipopolysaccharide for synthesis of factor B, but not C2, in human fibroblasts. J Exp Med 167:1-14

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