The alveolar macrophage (AM) is the sentinel phagocytic cell of the lung, performing essential antimicrobial, immunobiologic, and secretory functions within the alveolar units. Like other phagocytes, the AM is capable of generating reactive oxygen metabolites in response to phagocytic or soluble stimuli; this mechanism has been implicated as a mediator of acute lung injury in a variety of disorders. The elucidation of the mechanism by which the human AM mounts the respiratory burst is crucial in the understanding of both its normal microbicidal function and the pathogenesis of its mediation of acute lung injury. The extrapolation from precursor circulating human monocytes or comparison with animal AM's does not define the specific characteristics of initiating mechanisms, oxidative enzymology or stoichiometry of reactive oxygen-derived species found in the stimulated human AM parameters crucial for definition of AM-mediated damage. We endeavor to study 1) the mechanisms of activation of AM respiratory burst and the AM's specific stimulus response coupling, 2) the enzymatic apparatus responsible for the elaboration of toxic products of the burst by isolating constituent components and mechanistic studies, and 3) the character and quantity of a variety of reactive moieties initiated by the generation of superoxide or peroxide in the respiratory burst. The parallel yet important differences in oxidative activities already noted between human phagocytes suggest that such studies are appropriate and methodologically reasonable in deciphering the role the AM in lung injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033565-02
Application #
3345557
Study Section
(SRC)
Project Start
1984-09-30
Project End
1987-09-29
Budget Start
1985-09-30
Budget End
1986-09-29
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
Liou, L S; Sastry, R; Hartshorn, K L et al. (1994) Bovine conglutinin (BC) mRNA expressed in liver: cloning and characterization of the BC cDNA reveals strong homology to surfactant protein-D. Gene 141:277-81
Eggleton, P; Ghebrehiwet, B; Coburn, J P et al. (1994) Characterization of the human neutrophil C1q receptor and functional effects of free ligand on activated neutrophils. Blood 84:1640-9
Liou, L S; Sastry, R; Hartshorn, K L et al. (1994) Bovine conglutinin gene exon structure reveals its evolutionary relationship to surfactant protein-D. J Immunol 153:173-80
Eggleton, P; Lieu, T S; Zappi, E G et al. (1994) Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein. Clin Immunol Immunopathol 72:405-9
Wang, J S; Pavlotsky, N; Tauber, A I et al. (1993) Assembly dynamics of actin in adherent human neutrophils. Cell Motil Cytoskeleton 26:340-8
Hartshorn, K L; Sastry, K; Brown, D et al. (1993) Conglutinin acts as an opsonin for influenza A viruses. J Immunol 151:6265-73
Meers, P; Mealy, T; Tauber, A I (1993) Annexin I interactions with human neutrophil specific granules: fusogenicity and coaggregation with plasma membrane vesicles. Biochim Biophys Acta 1147:177-84
Bernardo, J; Brennan, L; Brink, H F et al. (1993) Chemotactic peptide-induced cytoplasmic pH changes in incubated human monocytes. J Leukoc Biol 53:673-8
Hartshorn, K L; Daigneault, D E; White, M R et al. (1992) Comparison of influenza A virus and formyl-methionyl-leucyl-phenylalanine activation of the human neutrophil. Blood 79:1049-57
Meers, P; Mealy, T; Pavlotsky, N et al. (1992) Annexin I-mediated vesicular aggregation: mechanism and role in human neutrophils. Biochemistry 31:6372-82

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