Identification of a substance, previously shown to enhance mitogenesis of human lymphocytes, as the acetamide of p-aminobenzoic acid.
We characterize here an arachidonic acid (AA)-derived metabolite previously found to have an adjuvant effect in phytohemagglutinin-induced mitogenesis of lymphocytes from mothers of newborn babies and from immunodeficient infants. We named the metabolite 'compound 4' due to its position in a thin-layer chromatography system developed for isolation of eicosanoids. The compound was originally found to be produced by peripheral blood mononuclear leukocytes and the T cell leukemia line Jurcat after long-term (18-24 h) incubation with [1-14C]AA. Compound 4 is also produced by lymphocytes, monocytes, platelets, thrombocytes, cultured fibroblasts and various types of malignant cell lines. We purified this metabolite by means of high pressure liquid chromatography with synchronous detection of radioactivity and measurement of ultraviolet-light absorption at 278 nm. Proton nuclear magnetic resonance spectroscopy and mass spectrometry with electron impact techniques demonstrated that compound 4 is not an eicosanoid, but is identical to p-acetamidobenzoic acid (PACBA). The cells synthesize PACBA from p-aminobenzoic acid and a two-carbon residue from AA.
Barbieri
B
B
Department of Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Papadogiannakis
N
N
Eneroth
P
P
Hansson
C
C
Roepstorff
P
P
Olding
L B
LB
D010129:4-Aminobenzoic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010835:Phytohemagglutinins / Q000494:pharmacology; D062366:para-Aminobenzoates
D010835:Phytohemagglutinins; D062366:para-Aminobenzoates; C023730:Acedoben; D016718:Arachidonic Acid; D010129:4-Aminobenzoic Acid