Increased Biosynthesis of Vasoactive Prostanoids in Schönlein-Henoch Purpura

Abstract

A8STRACT. Schonlein-Henoch purpura (SHP) is an acute immune-mediated vasculitis characterized by infiltration of polymorphonuclear leukocytes into the vessel wall causing damage to the vascular endothelium by the release of proteolytic enzymes. The local inflammatory and thrombotic process may be regulated by increased biosynthesis of vasoacti ve prostanoids. We investigated the biosynthesis of thromboxane A z (TxA z ), a potent vasoconstrictor and platelet agonist, prostacyclin (PGI z ), a vasodilator and platelet antagonist, and prostaglandin E z , a mediator of inflammation, in 14 children with SHP by physicochemical analysis of index metabolites in plasma and urine. TxA z and PGI2 biosynthesis in the systemic circulation was significantly elevated in the acute phase of the disease and correlated with the degree of clinical symptom s. Recurrent episodes of the disea se were associated with phasic increa ses of plasma and urinary TxA z and PGI z metabolites. Renal TxA 2 formation was highest in two patients presenting with the nephrotic syndrome and extracapillary glomerulonephritis. Pro staglandin E z biosynthesis in the systemic circulation was increased in the acute phase of the disea se. The enhanced TxAz formation is consistent with phasic platelet activation in SHP. The increased PGIz biosynthesis reflects endothelial cell damage and may be a response of vascular endothelium to modulate plateletvessel wall and leukocyte-vessel wall interactions. Increa sed prostaglandin E, formation, which probably derives from acti vated polymorphonuclear leukoc ytes and macrophages, is thought to be related to the inflammatory process in SHP. (Pediatr Res 32: 137-140, 1992 ) Abbreviations SHP, Schonlein-Henoch purpura SHP is the most com mon form of vasculitis in child ren (1). The vasculitis is initiated by the subendothelial deposition of IgA/IgG im m une complexes in small blood vessels (2). Complement activation induces infiltratio n of polym orph onuclear leukocytes, which by th e release of prot eolytic enzym es cause damage to th e vessel wall with secondary th rombosis and hem orrhage (3). Th e altered integrity of the vascular endothelium is likely to involve changes in prostanoid biosynthesis at the platelet vascular interface. Tx A 2 , the major cyclooxygenase product of ara chidonic acid in platelets, is a pot ent platelet aggregator and vasocon strictor (4). Th e potential pathophy siologic role of TxA 2 in acute immune-mediated vasculitic disorders has not yet been elucidated.In the present study, we investigated TxA z biosynthesis in childr en with SHP pros pectively during the disease process. To avoid sam pling and analytical probl em s, T xA z biosynthesis was examined by a highly specific and sensitive method, which measures two m ajor urinary enzymatic metabolites, I I-dehydroTx8 2 an d 2,3-dino r-TxB2, which are index metabolites of TxA 2 acti vatio n in th e systemic circulatio n (5, 6), and by measuri ng urin ary Tx B 2 , which predominantly reflects renal TxA 2 form ation (7). In addition , c...

Clinical outcome of Schönlein-Henoch purpura nephritis in children

“…Children with SHP nephritis have high levels of circulating IgA immune complexes, which may be related to an aberrant glycosylation of IgA [13,14]. Complement activation induces vascular infiltration by polymorphonuclear leukocytes and monocytes which, by the release of proteolytic enzymes, may cause damage to the endothelium with increased biosynthesis of vasoactive prostanoids [15].…”

Urinary prostacyclin metabolites in patients with IgA nephropathy

“…Although we did not examine TXA 2 production, which is generally evaluated by urinary TXB 2 excretion, TXA 2 production was reported to be enhanced in experimental nephritis and in patients with various renal diseases. [8][9][10][11][12][13][14][15] Therefore, it may be necessary to measure urinary TXB 2 and urinary PGI 2 metabolites simultaneously in order to estimate their imbalance.…”

“…IgAN is slowly progressive, and 30%-40% of IgAN patients developed end-stage renal failure during a 20-year observation. 6,7 Although renal and/or extrarenal PGI 2 biosynthesis have been investigated in various renal diseases, [8][9][10][11][12][13][14][15] urinary PGI 2 metabolites in patients with IgAN have not yet been sufficiently studied. In addition, to our knowledge, there is no previous report regarding the influence of prostacyclin production on the prognosis of renal disease.…”

Different Actions of the Cyclooxygenase 2 Selective Inhibitor Flosulide in Rats with Passive Heymann Nephritis

“…No difference in urinary prostaglandin excretion was seen in our study between control animals and untreated animals with PHN or after flosulide treatment. Elevated urinary prostaglandin excretion has been detected in other forms of glomerulonephritis [26]. Nagao et al [27]found a 5-fold increase in urinary thromboxane excretion in nephritic rats.…”