Inhibition of the classical and alternative pathways of the human complement system by glycosaminoglycan polysulfate.

Glycosaminoglycan polysulfate (GAGPS) concentration-dependently inhibited the activation of the classical and alternative pathways of the human complement system in vitro. Concentrations of > or = 0.2 mg/ml GAGPS prevented the cleavage of C4 by human aggregated gammaglobulin as evidence of inhibition of the classical pathway. At concentrations of > or = 0.15 mg/ml a concentration-dependent inhibition of the cleavage of factor B, the major step in the activation of the alternative pathway, was seen in the presence of inulin. Concentrations < 0.05 mg/ml did not have a measurable effect on either pathway. The lysis of sheep red blood cells, which is mediated largely by the classical pathway, was significantly inhibited at 3.84 mg/ml GAGPS, with a mean inhibition of 45.7%. On the other hand, the same concentration of GAGPS almost completely inhibited the lysis of rabbit red blood cells, which is mediated by the alternative pathway of complement. Our results suggest that the inhibition by GAGPS is an early event in the activation of complement, occurring before the assembly of the C3 convertases of either pathway. The possible use of this drug in acute life-threatening situations where complement is thought to have a pathogenic role is discussed.

Activation of human complement system in paracoccidioidomycosis.

Plasma samples of 14 patients with paracoccidioidomycosis were analysed for components that represent activation of the complement system. Most patients (12/13) showed significant titres of complement-fixing antibodies and 14/14 had increased C4d/C4 ratios. There was no conclusive correlation between these two immunological indices, however. Factor B values of patients were similar to normal donors and fragment Ba was not detected in any of the patients. These results indicate a classical complement pathway activation in the plasma of patients with paracoccidioidomycosis.

Complement activation in Brazilian pemphigus foliaceus.

Brazilian pemphigus foliaceus is an autoimmune blistering skin disease of man that has a very high incidence in a confined geographical distribution. Rocket immunoelectrophoresis of plasma showed increased levels of complement fragments, C4d and Ba, indicating activation of complement through both the classical and the alternative pathways. Less sensitive methods such as CH50, total C3 and C4 did not demonstrate this activation, and immune complex measurements were within normal range. While complement may not be absolutely necessary for the development of skin lesions, our longitudinal studies show that activation of complement is at its highest during the most active phase of the disease.

Complement and antibody deposition in Brazilian pemphigus foliaceus and correlation of disease activity with circulating antibodies.

Brazilian pemphigus foliaceus is a blistering skin disease endemic to central and southern areas of South America. In this study of skin biopsy specimens from 14 patients we present evidence that complement and immunoglobulins were present by direct immunofluorescence in the epidermal intercellular spaces in all patients. Eight of 14 patients had granular deposits of C3 in the basement membrane zone. By indirect immunofluorescence, serum samples from all 19 patients tested demonstrated the presence of circulating IgG autoantibody. Autoantibodies deposited in the intercellular spaces in titers ranging from 1:10 to more than 1:1280, and the titers drastically decreased during treatment. This is the first study to demonstrate complement deposition in the skin in Brazilian pemphigus foliaceus.

Bronchoalveolar lavage findings in pulmonary paracoccidioidomycosis.

Bronchoalveolar fluid cytology from six progressive pulmonary paracoccidioidomycotic patients showed an alveolitis of neutrophilic pattern which was independent of the of the duration of the chronic fungal disease. The percentage of neutrophils in paracoccidioidomycotic alveolitis was higher than in other neutrophilic alveolitis conditions.