Immune-complexes (IC) in idiopathic neutropenia.

The presence of immune-complexes (IC) and antipolymorphonuclear neutrophil (PMN) autoantibodies was investigated in 28 patients with chronic idiopathic neutropenia and normal or hypercellular bone marrow, 19 with a metamyelocyte arrest and 9 with more dysplastic features. The in vivo interaction between IC and PMN membrane receptors was evaluated by means of the PMN immunohistological technique. Circulating IC was evaluated with the C1q and rheumatoid factor agglutination inhibition techniques. An anti-PM autoantibody activity was investigated by challenging Fab obtained from the sera of 22 patients with PMN from normal donors. IC were detected in a high percentage of patients; in no case could an anti-PM autoantibody activity be seen. Most patients with a metamyelocyte arrest, but only 1 with more dysplastic features, were IC+. During a follow-up period of l2-52 months, none of the patients with a metamyelocyte arrest (IC+) developed anaemia, thrombocytopenia or leukaemia, while anaemia and thrombocytopenia were almost the rule in the clinical course of dysplastic bone marrow IC- patients: 2 of them developed acute myeloblastic leukaemia.

Mediators of immune-complex-induced aggregation of polymorphonuclear neutrophils. II. Platelet-activating factor as the effector substance of immune-induced aggregation.

Platelet-activating factor (PAF) is released in vitro during human and rabbit polymorphonuclear neutrophil (PMN) aggregation induced by C5a anaphylatoxin, neutrophil cationic proteins (CP) and their carboxypeptidase-B-derived fragments, C5a des Arg and CP des Arg, as well as phagocytosis of opsonized baker's yeast particles and immune complexes (IC). Purified PAF itself is able to cause in vitro PMN aggregation. By using selective inhibitors, we show that PMN aggregation, induced either by PAF or by other soluble stimuli such as C5a, CP and their des Arg products, follows a similar metabolic pathway, which is both adenosine-diphosphate-(ADP)- and arachidonic acid (AA)- independent. The in vivo injection of purified PAF into rabbits leads both to formation of intravascular PMN aggregates and to development of acute neutropenia, which has the same features as those observed after challenge with IC, C5a and CP. In this respect, electron-microscopic studies of intravascular PMN aggregates in the pulmonary capillary network and glomeruli show identical ultrastructural patterns. Moreover, the intravascular release of PAF is demonstrated after the intravenous injection of IC and temporally correlated with the development of neutropenia. We suggest that PAF is probably the final, common, effector substance of IC-, C5a-, C5a-des-Arg-, CP-, CP-des-Arg-mediated PMN aggregation.

[Hormonal modulation of inflammation]. / Modulazione ormonale dell'infiammazione.

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.

Mediators of immune complex-induced aggregation of polymorphonuclear neutrophils. I. C5a anaphylatoxin, neutrophil cationic proteins and their cleavage fragments.

This study reports the results of in vitro investigations on the aggregation of polymorphonuclear neutrophils (PMN) induced by the C5a anaphylatoxin complement component as well as the cationic proteins (CP), which are released by challenging PMN with immune complexes (IC). The carboxy-peptidase-derived des-Arg fragments of CP and C5a; CPi and C5ai, inactive in terms of anaphylactic and chemotactic activity, nevertheless showed a more potent ability to aggregate PMN than CP and C5a. The process of PMN aggregation required metabolic energy and divalent cations, Ca++ and Mg++. The microtubular system and the subplasmalemmal microfilaments appeared to be of critical importance. Electron microscopic studies on aggregates of PMN obtained on stimulation with CP, C5a, CPi and C5ai showed parallel tracts of variable length of cell membranes at the points where cells were in contact with each other.