[Clinical significance of reactive oxygen species]. / Klinische Bedeutung reaktiver Sauerstoffverbindungen.

There is increasing evidence that reactive oxygen substances are involved in the pathogenesis and/or progression of differ diseases. A short introduction to the biochemistry of reactive oxygen substances will be given in this review. Subsequently, the role of reactive oxygen substances will be discussed exemplarily on pathophysiological aspects of neutrophil granulocytes and of neurodegenerative diseases.

Unusual expression of IgG Fc receptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency).

Leukocyte adhesion deficiency (LAD) is a hereditary disease characterized by defective expression of leukocyte adhesion glycoproteins; lymphocyte function-associated Ag-1 (CD11a/CD18), CR3 (CD11b/CD18) and p150,95 (CD11c/CD18). Granulocytes, monocytes, and lymphocytes of patients with LAD show profoundly defective in vivo and in vitro adherence-dependent immune functions. We investigated the expression of FcR for IgG on polymorphonuclear cells (PMN) and monocytes from patients with LAD, and their luminol- and lucigenin-enhanced chemiluminescence production in response to SRBC sensitized with murine (m) IgG2a and IgG2b. Unstimulated patient PMN showed an enhanced chemiluminescence in response to mIgG2a-SRBC and an increased phagocytosis of mIgG2a-SRBC. The up-regulated functions were inhibited by monomeric human IgG in a dose-dependent manner, which was attributed to an increase in expression of FcRI on patient PMN, as shown by flow cytometry using monoclonal antibody, 32.2, specific for human FcRI. In contrast, neither the expression of FcR on the monocytes of LAD patients nor their FcR-mediated functions were different from those of controls.

[Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte function. II. Down's syndrome]. / Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione fagocitaria. Nota II. Sindrome di Down.

Numerous systemic syndromes with different aetiopathogenetic and clinical features are constantly accompanied by functional changes in polymorphonucleated neutrophils and, particularly, in their chemotactic properties. The function they perform, namely impeding invasion of the organism by external aggressive factors, cannot therefore be implemented. These patients are thus abnormally susceptible to infections and present a high frequency of serious periodontal disease.

[Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte function. III. Papillon-Lefevre syndrome]. / Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione fagocitaria. Nota III. Sindrome di Papillon-Lefèvre.

Numerous systemic syndromes with different aetiopathogenetic and clinical features are constantly accompanied by function changes in neutrophil polymorphoanucleates and, particularly, in their chemotactic properties. The function they perform, namely impeding the invasion of the organism on the part of aggressive external factors, cannot therefore be implemented. These patients are thus abnormally susceptible to infections and present severe periodontal disease with high frequency.

[Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte function. I. Diabetes mellitus]. / Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione fagocitaria. Nota I. Diabete mellito.

Diabetes mellitus is accompanied constantly by functional changes in polymorphonucleated neutrophils and particularly in their chemotactic properties. Their function of impeding the invasion of the organism on the part of aggressive external factors cannot therefore be implemented. These patients are, therefore abnormally susceptible to infection and, with high frequency, also present serious periodontal disease.

Chemotactic disorders.

Clinical disorders of phagocyte chemotaxis have heterogeneous etiologies. The physiologic defect can involve adherence, the cytoskeleton, deformability, granule dysfunction, regulation of receptors, or a variety of soluble mediators. At present, successful clinical management depends on early and compulsive attention to infectious complications. A host of new immunomodulators (GM-CSF, gamma interferon, tumor necrosis factor, etc.), made available through recombinant gene technology, are now under study and may provide new and more effective means of treatment for these life-threatening disorders.

[Clinical symptoms, diagnosis and treatment of phagocyte dysfunction]. / De klinische verschijnselen, diagnostiek en behandeling van fagocytenfunctiestoornissen.

When patients suffer from recurrent infections with bacteria or fungi that react poorly with the commonly prescribed antibiotics, phagocyte dysfunctions should be considered. In this article, a survey is given of the mechanism of action of these cells, the dysfunctions that may occur, the resulting clinical symptoms, the laboratory diagnostics and some therapeutical approaches.

Hyperoxia damages phagocytic defenses of neonatal rabbit lung.

The effect of hyperoxia on phagocytic defenses of neonatal rabbit lung was ascertained by exposure to a fractional inspired O2 concentration of 0.95 + or 0.21 for 48, 96, or 168 h. Intrapulmonary clearance of inhaled staphylococci was reduced by 67 and 74% after 96 and 168 h in hyperoxia (P less than 0.05). Impaired phagocytic killing was not due to diminished bacterial ingestion. Alveolar macrophages (AM) lavaged from pups reared in normoxia had a progressive ability to release superoxide (O-2) and showed increasing cyanide-sensitive O2 consumption during the 1st wk of life. Conversely, AM recovered from litters housed in hyperoxia for 48 h produced 190% more O-2 than normoxic controls (P less than 0.005), but this capacity to generate O-2 fell by 43% after 96 h of exposure (P less than 0.05). After 96 h of hyperoxia, AM had a significant shift toward cyanide-insensitive metabolism compared with normoxic cells (P less than 0.05). Polymorphonuclear leukocytes (PMN) entered the alveoli after 96 h of hyperoxia, and mortality rose abruptly in animals exposed for 168 h (16%) vs. 96 h (3%). Our findings indicate neonatal hyperoxia induces metabolic and bactericidal dysfunction in the primary pulmonary phagocyte, the AM, and this injury is followed by additional lung insult during PMN migration into the airways.

[Granulocyte function in Duchenne's progressive muscular dystrophy]. / La funzionalità granulocitaria nella distrofia muscolare progressiva di Duchenne.

We studied the in vitro function of polymorphonuclear leukocytes in 14 patients affected by Duchenne muscular dystrophy, aged 2-14 years, especially the chemotaxis and the bactericidal activity. The chemotaxis appeared significantly reduced, while the bactericidal activity was sometimes reduced, sometimes increased. In this disease the polymorphonuclear leukocytes seems to have a reduced capacity of movement; probably this phenomenon is connected with an alteration of the muscular cellular apparatus, which perhaps is related with an electrolytic intercellular inequality. These findings are consistent with the definition of Duchenne muscular dystrophy as a systemic disease of the membrane with alterations not only of striped muscular fibers, but of various cells and tissues.

[Current aspects of chemotaxis of phagocytic cells]. / Aspects actuels de la chimiotaxie des cellules phagocytaires.

Phagocytic cells, the first host defence against microbial attack, are remarkably mobile; they can move very rapidly to the infectious or inflammatory site. They migrate toward a chemotactic factor: C5a, lymphokines, bacterial products, leukotriene B4, etc. The binding of the chemotactic factor to its specific receptor on the cell leads to an activation of the phagocytic cell: the electric potential of the membrane changes, ionic fluxes and free calcium rate increase, arachidonic acid metabolites are produced, cyclic nucleotides are activated. This produces a change in shape, a polarization of the cell and, after cytoskeleton reorganization, migration of the cell towards the chemotactic factor. A constitutional or acquired abnormality of one of these steps induces a defect of chemotaxis for the phagocytic cells and severe infections.

Neutrophil dysfunction associated with states of chronic and recurrent infection.

Infants, children, and young adults who suffer chronic and recurrent bacterial or fungal infection despite adequate numbers of circulating granulocytes and normal or elevated levels of immunoglobulins should be suspected of having fundamental defects in granulocyte functioning. This article considers clinical disorders for which there is evidence for associated defects of polymorphonuclear leukocytes.