The adult respiratory distress syndrome (ARDS) is an acute deterioration of lung function in patients with severe underlying diseases such as sepsis. It is likely that neutrophil proteases and oxidants contribute to the severity of the lung disorder. Two peptides were identified which may be responsible for the secretion of enzymes from the neutrophils which enter the lungs. These peptides are the neutrophil activating factor (NAF) and the enzymereleasing peptide (ERP) . One of them, NAF, may also attract neutrophils into the lungs. These studies will determine if it is likely that these peptides play an important role in exacerbating the lung disorder in patients with ARDS. They will also determine why they occur, why they are active, and which agents facilitate their secretion and action. Ultimately, it is only by reducing their activity in these patients that their clinical importance will be known. Therefore, many of these studies will focus on developing means of counteracting their activity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043650-04
Application #
3362365
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1990-06-01
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas Health Center at Tyler
Department
Type
Other Domestic Higher Education
DUNS #
City
Tyler
State
TX
Country
United States
Zip Code
75708
Kurdowska, A; Carr, F K; Stevens, M D et al. (1997) Studies on the interaction of IL-8 with human plasma alpha 2-macroglobulin: evidence for the presence of IL-8 complexed to alpha 2-macroglobulin in lung fluids of patients with adult respiratory distress syndrome. J Immunol 158:1930-40
Miller, E J; Nagao, S; Carr, F K et al. (1996) Interleukin-8 (IL-8) is a major neutrophil chemotaxin from human alveolar macrophages stimulated with staphylococcal enterotoxin A (SEA). Inflamm Res 45:386-92
Miller, E J; Cohen, A B; Peterson, B T (1996) Peptide inhibitor of interleukin-8 (IL-8) reduces staphylococcal enterotoxin-A (SEA) induced neutrophil trafficking to the lung. Inflamm Res 45:393-7
Kurdowska, A; Miller, E J; Noble, J M et al. (1996) Anti-IL-8 autoantibodies in alveolar fluid from patients with the adult respiratory distress syndrome. J Immunol 157:2699-706
Miller, E J; Cohen, A B; Matthay, M A (1996) Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis. Crit Care Med 24:1448-54
Kurdowska, A; Miller, E J; Cohen, A B (1995) An anti-interleukin 8 monoclonal antibody that interferes with the binding of interleukin 8 to cellular receptors and the activation of human blood neutrophils. Hybridoma 14:225-33
Miller, E J; Cohen, A B; Carr, F K et al. (1995) High yields of interleukin-8 produced by a synthetic gene expressed in Escherichia coli and purified with a single antibody affinity column. Protein Expr Purif 6:357-62
Hayashi, S; Kurdowska, A; Miller, E J et al. (1995) Synthetic hexa- and heptapeptides that inhibit IL-8 from binding to and activating human blood neutrophils. J Immunol 154:814-24
Kurdowska, A; Cohen, A B; Carr, F K et al. (1994) Biological and kinetic characterization of recombinant human macrophage inflammatory peptides 2 alpha and beta and comparison with the neutrophil activating peptide 2 and interleukin 8. Cytokine 6:124-34
Griffith, D E; Miller, E J; Gray, L D et al. (1994) Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells. Am J Respir Cell Mol Biol 10:245-52

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