Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes.
Theta-defensins are macrocyclic antimicrobial peptides that were previously isolated from leukocytes of a single species, the rhesus macaque. We now report the characterization of baboon theta-defensins (BTDs) expressed in bone marrow and peripheral blood leukocytes. Four cDNAs encoding theta-defensin precursors were characterized, allowing for the prediction of 10 theoretical theta-defensins (BTD-1 to BTD-10) produced by binary, head-to-tail splicing of nonapeptides excised from paired precursors. Five of the predicted theta-defensins were purified from baboon leukocytes, and synthetic versions of each were prepared. Anti-theta-defensin antibody localized the peptides in circulating neutrophils and monocytes and in immature and mature myeloid elements in bone marrow. Each of the BTDs possessed antimicrobial activity against bacterial and fungal test organisms in vitro. Peptide activities varied markedly despite a high degree of sequence conservation among the theta-defensins tested. Thus, baboons express numerous theta-defensins which appear to differentially contribute to host defense against diverse pathogens.
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697-4800, USA.
Angie E
AE
Garcia
George
G
Osapay
Patti A
PA
Tran
Jun
J
Yuan
Michael E
ME
Selsted
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D023082:Defensins / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D010215:Papio / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D023082:Defensins; D020033:Protein Isoforms; C450142:theta-defensin