Platelet-activating factor (PAF) in experimentally-induced rabbit acute serum sickness: role of basophil-derived PAF in immune complex deposition.
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Biomedical subjects
Publications and source records attributed to A Vercellone.
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In addition to a hemorrhagic diathesis, uremia is accompanied by a clotting tendency, caused by a marked fall in fibrinolytic capacity. Measurement of lysis time of whole blood diluted with phosphate and acetate buffers and of euglobulin lysis times showed that accumulation of inhibitors is primarily responsible. These probably belong to the class of small molecules abnormally retained in uremia. Hemodialysis (HD) offers the best method of correction, mainly because of better elimination of these inhibitors. In contrast, hemofiltration (HF) and, particularly, intermittent peritoneal dialysis (IPD) are much less effective. In IPD, protein loss via the peritoneum is also responsible for a loss of fibrinolytic activators, so that fibrinolysis becomes even poorer, exposing the patient to an increased risk of vascular complications.
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The ability of basophils and tissue mastocytes activated by sensitised IgE antibodies to release mediators in the presence of the specific antigen underlies immediate hypersensitivity reactions. This phenomenon can be explored by the in vitro basophil degranulation test adopted not only in experimental pathology, but in human allergological pathology and in the study of post-streptococcal and lupus glomerulonephritis. The test has been carried out to analyse sensitisation to iodate contrast media in 71 patients already submitted to contrastography, 37 of whom had given evidence of allergic reactions. All patients with a previous history of sensitisation presented, in vitro, a positive reaction (56 + 15.3% degranulation) in the presence of the contrast medium. Against this, none of the patients with negative test presented an allergic reaction during contrastography. Stress is laid on the practical importance of the test prior to performance of contrastography so as to predict possible sensitisation and select the most suitable medium.
In spite of the anticoagulant activity of heparin platelet deposition and contact activation of coagulation occurs during dialysis. We have studied platelet counts, fibrinogen, platelet factor 4, beta-thromboglobulin, thromboxane B2, FRA, C3d and kallikrein values, whole blood and euglobulin lysis times and membrane areas in haemodialysis using cuprophan and cellulose acetate and in haemofiltration with polyacrilonitrile. Deposits on all the three membranes included leucocytes, platelets and fibrin. The coagulation and fibrinolytic systems are activated more intensively with cellulose acetate and more prolongedly with polyacrilonitrile. Platelet factor 4 and beta-thromboglobulin increases suggest platelet activation, only partially dependent on arachidonic acid-mediated pathway as thromboxane B2 is not increased. The complement system is activated whereas serum kallikrein does not alter, suggesting that platelets rather than factor XII are crucial in contact activation.
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Haematochemical, urinary and tissue parameters were examined in the elaboration of the coagulation and fibrinolysis profile in 33 cases of systemic lupus erythematosus in different stages of the disease. Coagulation abnormalities varied from hypo- to hyper-coagulability, these being often associated in the same patient, either simultaneously or at different stages of the disease. Activation of coagulation, closely related to the immunological activity of the disease, was present in 80% cases in the acute stage, and 36% of those in the remission stage. The lupus-like anticoagulant was not much involved, and platelets were the prime figures in the haemostatic abnormalities of lupus, those being the preferred target of direct antibody activities, or possibly of immune complexes as well. Activation of the coagulatory cascade is not uncommonly accompanied by a thrombophilic tendency coupled with signs of consumption, this being the expression of a continuously stimulated haemostatic balance.
The tissue damage during the inflammation is determined by the enzymes and the mediators of anaphylaxis released from polymorphonuclear cells (PMN), platelets, basophils and mastocytes. The control of this release involves the cAMP and cGMP. The cyclic nucleotides independently or synergically regulate the polymerisation of the microtubules and the microfilaments. Drugs increasing the intracellular concentration of cAMP or cGMP inhibit or enhance respectively the enzymatic release from PMN, basophils and mastocytes. In the platelets, cAMP plays a very important role, whereas the cGMP function is controversial.
Twenty-nine patients with Systemic Lupus Erythematosus (SLE) and 6 patients with Acute Poststreptococcal Glomerulonephritis (APGN) have been studied with the polymorphonuclear neutrophil (PMN) immunohistological technique to detect in vivo interaction between circulating immune complexes (IC) and PMN membrane receptors. Patients have been studied both at diagnosis and during follow-up and the results compared to those yielded by the C1qSP test. Our data provide evidence that the PMN immunohistological technique may prove a useful tool in monitoring IC disease. Moreover, elution studies may allow the detection and characterization of the antigens in the PMN-bound IC.
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Neutrophils (PMN) appear to be involved in inflammatory phenomena as a result of direct interaction with immune complexes (IC). In SLE glomerulonephritis IC are fixed in vivo on the PMN surface through the receptors for FC fragments of complexed immunoglobulins and complement. Phagocytic properties are lost and immunological lysosomal release in vitro is markedly reduced by virtue of receptor occupation. The elimination of neutrophil cationic proteins (NCP) in urine is an expression of PMN lysosomal constituent release.