1-Peptidyl-2-arachidonoyl-3-stearoyl-sn-glyceride: an immunologically active lipopeptide from goat serum (Capra hircus) is an endogenous damage-associated molecular pattern.
Experiments were undertaken to isolate a component of the serum of goat (Capra hircus) that is effective at mediating an innate immune response. This report describes the isolation and structure elucidation of 1-(N-acetyl-ALYDKGYTSKEQKDCVGI)-2-arachidonoyl-3-stearoyl glyceride (1) and its immunomodulatory activity. A dose-response relationship for inflammatory cytokine and chemokine production and release from human fibroblasts incubated with nanomolar concentrations of 1 was shown. Moreover, the membrane transport role of the diacylglycerol moiety in 1 is demonstrated with nanomolar quantities of the transfected N-acetyl peptide moiety of 1 also inducing inflammatory cytokine and chemokine production and release. The apparent EC99 for 1 was 3 ng/mL (1 nM). The likely biological role for naturally occurring 1 as a damage-associated molecular pattern is postulated.
Thacker
James D
JD
TherimuneX Pharmaceuticals, Inc., Doylestown, Pennsylvania 18902, USA. jim_thacker@therimunex.com
Brown
Martyn A
MA
Rest
Richard F
RF
Purohit
Mitali
M
Sassi-Gaha
Sihem
S
Artlett
Carol M
CM
D000595:Amino Acid Sequence; D000818:Animals; D000829:Animals, Domestic; D004305:Dose-Response Relationship, Drug; D006041:Goats; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D016209:Interleukin-8 / Q000032:analysis; D055666:Lipopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D015394:Molecular Structure; D012689:Sequence Homology, Nucleic Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C545397:1-(N-acetyl-ALYDKGYTSKEQKDCVGI)-2-arachidonoyl-3-stearoyl glyceride; D007155:Immunologic Factors; D016209:Interleukin-8; D055666:Lipopeptides