The Activity of Polymorphonuclear Leukocyte Neutral Proteinases and Their Inhibitors in Patients with Psoriasis Treated with a Continuous Peritoneal Dialysis

Abstract

3 of 16 patients with extensive psoriasis have been completely cleared of skin lesions within 2-3 weeks of continuous peritoneal dialysis, and 2 of them up to 2 mo after termination of therapy. In 5 cases there was a great improvement of psoriatic lesions and in 6 remaining cases only a slight improvement was found. The remission of psoriasis was correlated with extremely high polymorphonuclear leukocyte depletion through the peritoneal cavity in a short time. Neutral serine proteinases were extracted from polymorphonuclear leukocytes and quantitated. The quantity of enzymes in the cells recovered from peritoneal dialysates was found to decrease with duration of treatment, and it was 2-5 times lower than amounts of neutral proteinases extracted from peripheral blood polymorphonuclear leukocytes of psoriatics and normals. The enzyme content per polymorphonuclear leukocyte of patients with active psoriasis was significantly higher (2-fold) than that in inactive psoriasis and in normal controls. Proteinase activity was also found in the sera of psoriatics and normals, as well as in the peritoneal dialysates. However, this activity appeared to be about 30-50 times lower than serum inhibitory activity against neutral proteinases. The concentration of neutral proteinase inhibitors in 5 of 17 sera of patients with psoriasis was significantly lower than that in normal sera. These data indicate that the depletion of activated PMNL with increased amounts of neutral proteinases may account for the beneficial effect of peritoneal dialysis in the clearing of psoriatic lesions.

In vitro Effects of Enzymes of Polymorphonuclear Leukocytes on the Antigenicity of Stratum corneum

“…The highest increase was observed in enzyme concentration of 1 6 x l0 -2 pu/ml; the titration endpoint was not reached in that experiment. The effects of the PMN extract on the SC was inhibited by DFP (5 mg/ml) and by PMSF (1 x 10 M) in control experiments, the results of which have been published previously [8,9].…”

“…but not p-chloromercuribenzoate]. Other studies [8,9] reveal that these extracts contain two NSP, notably elastase and cathepsine G.…”

“…Chymotrypsin served as a control, since this enzyme has biochemical characteristics similar to those of the NSPof PMN [8].…”

“…The increased amount of neutral serine proteinase (NSP) in peripheral blood PMN was found in pa tients with active psoriasis but not in those with inac tive disease or in normal controls [8], This enzyme, ex tracted from PMN with citrate buffer of pH 3.2, was capable, after neutralization, of destroying the archi tecture of SC of both psoriatic and normal epidermis [7], However, despite the massive damage to the SC of psoriatic lesion, IgG and C3 deposited in vivo in the SC were not digested and could be identified by direct immunofluorescence.…”

Migration of Polymorphonuclear Leukocytes in Psoriasis

“…Chemotactic responsiveness in psoriatics was found normal [24, 56, 57], increased [58][59][60][61][62][63] and decreased [64]. Activ ities of neutral serine proteases in psoriasis have been reported to be increased [65] and normai [66], A remarkable association of PMN functions with the clinical manifesta tion of psoriasis has been shown by Glinski et al [67]. Increased activities of neutral pro teases and other PMN enzymes were found in patients who happened to be in a state of exacerbation, normal activities were ob served in the chronic stable plaque form and decreased activities were measured in pso riatics with regressing lesions.…”