A New Function of Human Haptoglobin: Endogenous Inhibition of Prostaglandin Biosynthesis and its Relation to Haemoglobin Binding

摘要

Human haptoglobin (Hp) is a glycoprotein present in plasma or serum which has the capacity to bind hemoglobin (Hb) specifically and stoichiometrically. Since Hb stimulates prostaglandin (PG) synthase, we investigated the possibility that Hp might affect PG synthesis by combining with Hb. Human Hp was purified by extraction, ammonium sulphate fractionation and DEAE-ion exchange chromatography. The results showed that Hp (50-250 μg protein) selectively inhibited in a concentration-related manner, the biosynthesis of PGs via cyclooxygenase pathway. Hp also inhibited lipoxygenase pathway of arachidonic acid metabolism in a concentration related manner. Additional evidence that Hp inhibited PG biosynthesis was obtained by I) the loss of Hp inhibitory activity upon removal of Hp by affinity chromatography on hemoglobin-sepharose from a sample of purified Hp or plasma, ii) inhibiton by Hp of arachidonic acid or bradykinin-induced bronchoconstriction in the guinea-pig and iii) inhibition of arachidonic acid-induced tone of the rat gastric fundus strip. Hb (a known stimulant of cyclooxygenase) reduced the inhibitory effect of Hp in a concentration-related manner, such that all its inhibitory property was lost when it was completely bound by Hb. These findings point to a new function of Hp: endogenous regulation of PG synthesis by combining with Hb release during injury (thus inflammatory processes). Therefore, mammals have dual defence system i.e. a specific immune system and non-specific Hp defence system.