DISTRIBUTION OF LACTOFERRIN AND 60 65 KDA HEAT-SHOCK PROTEIN IN NORMAL AND INFLAMED HUMAN INTESTINE AND LIVER/

Immunisation against the mycobacterial heat shock protein (hsp-65) has been proposed to lead to production of autoantibodies against human l actoferrin. Such antibodies occur in ulcerative colitis and in primary sclerosing cholangitis. This study analysed the distribution of hsp-6 5 and lactoferrin in biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis and studied whether i mmunisation against mycobacterial hsp-65 resulted in production of ant ilactoferrin antibodies and vice versa. Polyclonal rabbit antihuman la ctoferrin and monoclonal mouse anti-hsp-65 (ML30) were used for immuno histochemistry on biopsy specimens from patients with inflammatory bow el disease and primary sclerosing cholangitis. Rats were immunised aga inst human lactoferrin and mycobacterial hsp-65 respectively. Antibody measurements were done by enzyme immunosorbent assays. It was found t hat lactoferrin and hsp-60/65 were not codistributed. Lactoferrin was found on vascular endothelium and in nonparenchymal liver cells both i n inflamed and uninflamed tissues, but only in the hepatocytes of infl amed liver. ML30 reactivity was not inhibited by antilactoferrin antib odies. Rat anti-hsp-65 serum had no detectable antilactoferrin antibod ies. In conclusion, antilactoferrin antibodies probably do not arise b y immunisation against mycobacterial hsp-65. Both nonparenchymal cells and hepatocytes probably participate in clearance of lactoferrin. End othelial exposure of lactoferrin may have pathogenic implications in d iseases with antilactoferrin autoantibodies.