Serum samples from patients with active psoriasis enhance lymphocyte-induced angiogenesis and modulate endothelial cell proliferation.

In former studies we have shown the increased angiogenic capability of peripheral blood mononuclear cells (MNCs) from patients with the active guttate type of psoriasis vulgaris. The present study tested the effects of serum factors from 67 patients with various forms of psoriasis vulgaris and from 32 healthy individuals on the angiogenic capability of normal human MNCs in an animal system. The angiogenesis-enhancing effect was most marked in the serum samples from patients with plaquelike and peripherally spreading lesions lasting for one to two months, and tended to disappear in patients with long-lasting and/or stationary lesions. Serum samples from patients with psoriasis were also capable of modulating the proliferation of normal human endothelial cells in vitro, and this modulation was correlated with the duration of relapse. The effects of psoriatic sera on normal human MNC function and on endothelial cell growth may be of importance for vascular proliferation in psoriasis.

Decreased extracellular release of granule enzymes from in vitro-stimulated polymorphonuclear leukocytes in guttate psoriasis.

In vitro degranulation of polymorphonuclear leukocytes, which were stimulated either with synthetic chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine, FMLP) or with C3b-opsonized zymosan as a promotor of phagocytosis, was studied in 66 patients with psoriasis, 18 lesion-free psoriatics, 18 healthy subjects, and 14 other dermatological disorder controls. Stimulated release of lysozyme (from specific granules and azurophil granules) and beta-glucuronidase (from azurophil granules) in the presence of both FMLP and serum-activated zymosan was markedly reduced in patients with actively spreading guttate psoriatic lesions, in whom relapse of lesions lasted for less than 1 month and papules involved about 13-25% of skin surface. In contrast, stimulated degranulation was within normal range in active plaque psoriasis, stationary plaque psoriasis, symptomless psoriatics, and patients with disseminated eczema. Spontaneous release of lysozyme and beta-glucuronidase (background) was found to be not different in all groups studied; however, patients with active guttate psoriasis had significantly lower total lysozyme activity than those with active and stationary plaque psoriasis as well as psoriatics in the remission. These data are in favor of in vivo activation of neutrophils in active guttate psoriasis by some factors related to the early relapse of the lesions. This results in a possible combination of the following phenomena: (1) in vivo partial degranulation of neutrophils; (2) induction of "unresponsiveness state" of these cells to subsequent in vitro stimulation; and/or (3) migration of highly responsive neutrophils to skin lesions, which leaves in the circulation the subpopulation less reactive to chemotactic and phagocytic stimuli.

Leukopheresis for treatment of psoriasis: is therapeutical benefit related to reduced activities of neutral proteinases of polymorphonuclear leukocytes?

Ten patients were treated with repeated leukophereses performed one to three times per week for 2-5 weeks. Two of the patients was cleared completely, four exhibited regression of more than one-half of the lesions, and four showed only a slight improvement. The therapy did not markedly affect the granulocyte count in peripheral blood, and the beneficial clinical response was not related to the number of polymorphonuclear leukocytes (PMNs) removed by leukophereses. During therapy, the activities of elastase, cathepsin G, lysozyme, and myeloperoxidase in PMNs were determined by spectrophotometry. PMNs isolated using a Haemonetics 30 blood-cell separator were about 50% deficient in these activities in comparison to cells obtained directly from peripheral blood. Thus, leukopheresis induces a marked degranulation of PMNs. Repeated leukophereses were found to generate significant variations in the activities of circulating PMN granule enzymes and in the levels of acid-soluble proteins. Remission or great improvement were observed in patients who, during therapy, exhibited decreased PMN elastase and cathepsin G activities, whereas a poor clinical response was accompanied by high enzymatic activities.

Neutral proteinases and other neutrophil enzymes in psoriasis, and their relation to disease activity.

The activities of elastase, cathepsin G, lysozyme and myeloperoxidase of polymorphonuclear leukocytes were determined by spectrophotometry in thirty-six patients with psoriatic lesions, twelve symptom-free patients with psoriasis and fifteen normal controls. The mean activities of cathepsin G, elastase and lysozyme were found to be increased by 55 to 70% in patients with actively spreading plaque lesions compared with healthy controls (P less than 0.01). Most patients with guttate lesions had total enzyme activities within the normal range. Those with stationary plaque psoriasis had activities of both neutral proteinases (cathepsin G and elastase) which were about 40% lower than normal controls (P less than 0.05). In the lesion-free psoriatics, the activities of neutral proteinases were about 70% of control values. Our findings emphasize the importance of assessment of disease activity in this sort of investigation. The present data may help to resolve much of the confusion regarding PMN function in psoriasis.

Chemical identification of some cell-wall components of microorganisms isolated from human leprosy lesions.

The cell walls of 24 coryneform non-acid-fast, Gram-positive organisms isolated from human leprosy lesion, were hydrolysed and analysed. Four known chemical markers of different high polymer components of the walls of microorganisms of the CMN (Corynebacterium, Mycobacterium, Nocardia) group were detected in whole cells and cell wall hydrolysates of the coryneform bacteria analyzed. These markers were: meso-diaminopimelic acid (peptidoglycan), arabinose and galactose (arabinogalactan), and mycolic acids. In addition, mycolic acids proved to be of the corynomycolic type, as shown by thin layer chromatography analysis. The conclusion was drawn that these coryneform strains independently isolated from patients of different countries, represent a homogeneous group within the genus Corynebacterium. This inference is supported by a parallel work showing that the guanine-plus-cytosine content of the DNA of these coryneform strains falls within the range of values characteristic of true corynebacteria pathogenic for animals.

Primary structure of the wall peptidoglycan of leprosy-derived corynebacteria.

The cell walls isolated from axenically grown leprosy-derived corynebacteria were submitted to various chemical and enzymatic degradations. The glycan strands of the wall peptidoglycan are essentially composed of N-acetylglycosaminyl-N-acetylmuramic acid disaccharide units. Small amounts of N-acetylglycosaminyl-N-glycolylmuramic acid (less than 10%) were also detected. The muramic acid residues of adjacent glycan strands are substituted by amidated tetrapeptide units which, in turn, are cross-linked through direct linkages extending between the C-terminal D-alanine residue of one tetrapeptide and the mesodiaminopimelic acid residue of another tetrapeptide. Such a structure is very similar to that of the wall peptidoglycan found in the taxonomically related microorganisms of the Corynebacterium, Mycobacterium, and Nocardia groups.

Phage-dependent changes in Shigella flexneri type antigen synthesis.

Lysogenic conversion of Shigella flexneri type antigens was studied with the aid of wild-type and thermosensitive mutant phages. With all wild-type phages, the appearance of glycosylated antigen was accompanied by the appearance of polyprenyl phosphate glucose synthetase activity. With some of the mutant phages, the appearance of glycosylated antigen was not followed by the formation of lipid-linked glucose in the enzyme assay. The reverse has also been observed, i.e., the high rate of formation of lipid-linked glucose and the lack of V-type antigen.

Formation of polyisoprenol phosphate glucose in Shigella flexneri.

Lipid-linked glucose is formed from uridine diphosphate-glucose and ficaprenol phosphate only in strains of Shigella flexneri with glucosylated O antigen.