Further studies will be carried out on oxygen-dependent killing mechanisms of neutrophils. The respiratory burst oxidase from stimulated neutrophils will be purified and characterized, paying particular attention to the role of cytochrome b558 in its activity. Cloning of the gene for the 67K component of the oxidase will be initiated using probes prepared from peptide sequences determined on the purified material. Antibodies will be raised to the oxidase and used for studying the structure of the enzyme, its ontogeny and its occurrence in other cells. Studies will also be continued on the mechanisms of mutagenesis in bacteria that have been exposed to activated neutrophils.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI024227-06
Application #
3481280
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1986-03-01
Project End
1993-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Johnson, Jennifer L; Brzezinska, Agnieszka A; Tolmachova, Tanya et al. (2010) Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic 11:533-47
Brzezinska, Agnieszka A; Johnson, Jennifer L; Munafo, Daniela B et al. (2009) Signalling mechanisms for Toll-like receptor-activated neutrophil exocytosis: key roles for interleukin-1-receptor-associated kinase-4 and phosphatidylinositol 3-kinase but not Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF). Immunology 127:386-97
Munafo, Daniela B; Johnson, Jennifer L; Brzezinska, Agnieszka A et al. (2009) DNase I inhibits a late phase of reactive oxygen species production in neutrophils. J Innate Immun 1:527-42
Brzezinska, Agnieszka A; Johnson, Jennifer L; Munafo, Daniela B et al. (2008) The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic 9:2151-64
Catz, Sergio D (2008) Characterization of Rab27a and JFC1 as constituents of the secretory machinery of prostate-specific antigen in prostate carcinoma cells. Methods Enzymol 438:25-40
Munafo, Daniela B; Johnson, Jennifer L; Ellis, Beverly A et al. (2007) Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes. Biochem J 402:229-39
Pacquelet, Sandrine; Johnson, Jennifer L; Ellis, Beverly A et al. (2007) Cross-talk between IRAK-4 and the NADPH oxidase. Biochem J 403:451-61
Johnson, Jennifer L; Ellis, Beverly A; Munafo, Daniela B et al. (2006) Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes. BMC Immunol 7:28
DeLano, Frank A; Parks, Dale A; Ruedi, Julie M et al. (2006) Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously hypertensive rat. Microcirculation 13:551-66
Johnson, Jennifer L; Ellis, Beverly A; Noack, Deborah et al. (2005) The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase. Biochem J 391:699-710

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