PHOSPHOLIPASE A(2) ACTIVATING PROTEIN AND IDIOPATHIC INFLAMMATORY BOWEL-DISEASE

Background-Crohn's disease and ulcerative colitis are idiopathic infla mmatory bowel diseases (IBD) involving synthesis of eicosanoids from a rachidonic acid (AA), which is released from membrane phospholipids by phospholipase A(2) (PLA(2)). A potentially important regulator of the production of these mediators is a protein activator of PLA(2), refer red to as PLA(2) activating protein (PLAP). Aims-The purpose of this i nvestigation was to discover if PLAP values might be increased in the inflamed intestinal tissue of patients with IBD and in intestinal tiss ue of mice with colitis. Patients-Biopsy specimens were taken from pat ients wtih ulcerative colitis and Crohn's disease undergoing diagnosti c colonoscopy, and normal colonic mucosa was obtained from patients wi thout IBD after surgical resection. Methods-Immunocytochemistry with a ffinity purified antibodies to PLAP synthetic peptides was used to loc ate PLAP antigen in sections of intestinal biopsy specimens from IBD p atients compared with that of normal intestinal tissue. Northern blot analysis with a murine [P-32] labelled plap cDNA probe was performed o n RNA extracted from the colons of mice fed dextran sulphate sodium (D SS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS). Resu lts-PLAP antigen was localised predominantly within monocytes and gran ulocytes in intestinal tissue sections from IBD patients, and addition al deposition of extracellular PLAP antigen was associated with blood vessels and oedema fluid in the inflamed tissues, In contrast, tissue sections from normal human intestine were devoid of PLAP reactive anti gen, except for some weak cytoplasmic reaction of luminal intestinal e pithelial cells. Similarly, colonic tissue from DSS treated mice conta ined an increased amount of PLAP antigen compared with controls. The s troma of the lamina propria of the colonic mucosa from the DSS treated mice reacted intensely with antibodies to PLAP synthetic peptides, wh ile no reaction was observed with control mouse colons. These data wer e supported by northern analysis which showed that PLAP mRNA was incre ased in the colons of DSS treated mice and cultured HT-29 cells expose d to LPS. Conclusions-As PLAP values were increased in the intestinal mucosa of IBD patients and mice with colitis, as well as in LPS treate d cultured HT-29 cells, a role was postulated for PLAP in increasing P LA(2) activity, which leads to the increased synthesis of eicosanoids in intestinal tissues of patients with these inflammatory diseases.