muramidase and Psoriasis

Psoriasis is a T-cell-mediated skin autoimmune disease characterized by the aberrant activation of dermal dendritic cells (DCs) and the sustained epidermal expression of antimicrobial peptides. We have previously identified a link between these two events by showing that the cathelicidin antimicrobial peptide LL37 has the ability to trigger self-nucleic acid mediated activation of plasmacytoid DCs (pDCs) in psoriatic skin. Whether other cationic antimicrobial peptides exert similar activities is unknown. By analyzing heparin-binding HPLC fractions of psoriatic scales, we found that human beta-defensin (hBD)2, hBD3, and lysozyme are additional triggers of pDC activation in psoriatic skin lesions. Like LL37, hBD2, hBD3, and lysozyme are able to condense self-DNA into particles that are endocytosed by pDCs, leading to activation of TLR9. In contrast, other antimicrobial peptides expressed in psoriatic skin including elafin, hBD1, and psoriasin (S100A7) did not show similar activities. hBD2, hBD3, and lysozyme were detected in psoriatic skin lesions in the vicinity of pDCs and found to cooperate with LL37 to induce high levels of IFN production by pDCs, suggesting their concerted role in the pathogenesis of psoriasis.

Topics: Antimicrobial Cationic Peptides; beta-Defensins; Cathelicidins; Dendritic Cells; DNA; Gene Expression Regulation; Humans; Langerhans Cells; Muramidase; Psoriasis; Self Tolerance; Signal Transduction; Skin; T-Lymphocytes; Toll-Like Receptor 9

We compared the salivary immunoglobulin A (IgA) and lysozyme concentration and secretion rates among mild and severe psoriasis patients and controls in Singapore.. Fifty-one psoriasis patients and 24 controls participated in the study. None of the patients were on immunosuppressive therapy. The Psoriasis Area and Severity Index (PASI) was used to assess the severity of psoriasis. Patients were divided into mild and severe groups by the median PASI score. Each subject contributed a 5-minute unstimulated salivary sample. Enzyme-linked immunosorbent assay method was used to determine the salivary IgA and lysozyme levels.. Psoriasis patients had lower concentration and secretion rate of IgA (geometric mean [GM], 97.5 micro g/mL and 32.3 micro g/min) and lysozyme (GM, 127.6 micro g/mL and 42.1 micro g/min) than controls (IgA GM 256.3 micro g/mL, 79.1 micro g/min; lysozyme GM 180.9 micro g/mL, 55.8 micro g/min) [P = 0.000 (IgA concentration), P = 0.000 (IgA secretion rate), P = 0.015 (lysozyme concentration) and P = 0.150 (lysozyme secretion rate)]. However, no significant differences were observed between mild and severe patients for both IgA and lysozyme concentrations and secretion rates. PASI score showed negative, but non-significant, correlations with either log salivary IgA (r = -0.22, P = 0.13) or log lysozyme (r = -0.09, P = 0.53) secretion rates.. Psoriasis patients had lower concentrations and secretion rates of salivary IgA and lysozyme compared to controls. However, among patients, the salivary IgA and lysozyme levels are variable and not related to severity of psoriasis.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin A, Secretory; Male; Muramidase; Psoriasis; Saliva

The distribution of lysozyme was investigated in psoriatic skin lesions, perilesional skin and in skin from healthy controls, using the immunoperoxidase techniques avidin-biotin complex and alkaline phosphatase-anti alkaline phosphatase. Lysozyme was identified in polymorphonuclear leukocytes present in the Munro microabscesses and also occasionally in other parts of the skin, as shown by very strong cytoplasmic staining. Stratum corneum, stratum granulosum and stratum spinosum were weakly stained. In some cases positive staining along the dermal collagen bundles was demonstrated and is most likely to be related to the number of inflammatory cells in the papillary dermis. Psoriatic skin lesions stained significantly stronger for lysozyme than did perilesional skin (p < 0.0001), whereas skin from healthy controls stained weakly positive or was lysozyme negative. Lysozyme may be of some importance in the psoriatic disease process. By comparison the alkaline phosphatase-anti-alkaline phosphatase was found to be the most specific of the two techniques.

Topics: Adult; Humans; Immunohistochemistry; Middle Aged; Muramidase; Psoriasis; Skin

Significantly lower lysozyme concentrations were found in saliva of 15 psoriatic patients compared with controls, whereas in serum, lysozyme activity, was significantly higher than in controls. The concentrations of IgA in serum of psoriatic patients were significantly higher than in controls, whereas in patients' saliva IgA concentrations were not significantly different from the controls. The findings indicate that lysozyme and IgA may be of significance in the pathophysiology of psoriasis.

Topics: Adult; Humans; Immunoglobulin A; Middle Aged; Muramidase; Psoriasis; Saliva

Topics: Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Biomarkers; Focal Infection; Giant Cells; Hyperplasia; Immunohistochemistry; Muramidase; Psoriasis; S100 Proteins; Tonsillitis

Blood serum and salivary characteristics of immunobiologic reactivity were examined in children suffering from psoriasis. Increased blood serum levels of IgG and lowered IgM were detected. Lysozyme and complement levels were increased both in the blood serum and saliva.

Topics: Adolescent; Child; Child, Preschool; Complement System Proteins; Female; Humans; Immunoglobulins; Male; Muramidase; Psoriasis; Saliva

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.

Topics: Cells, Cultured; Chemotaxis, Leukocyte; Complement C3; Cytoplasmic Granules; Eczema; Glucuronidase; Humans; Muramidase; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Photosensitivity Disorders; Psoriasis; Zymosan

Macrophages derived from circulating blood monocytes of psoriatic patients demonstrated an enhanced release of beta-glucuronidase and lysozyme compared with macrophages from healthy subjects. The relationship of cell activation to the pathogenesis of psoriasis is discussed.

Topics: Female; Glucuronidase; Humans; L-Lactate Dehydrogenase; Macrophages; Male; Muramidase; Psoriasis

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.

Topics: Adult; Cathepsin G; Cathepsins; Endopeptidases; Female; Humans; Leukapheresis; Male; Middle Aged; Muramidase; Neprilysin; Neutrophils; Pancreatic Elastase; Peroxidase; Psoriasis; Serine Endopeptidases

The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IgG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and beta 2-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P less than 0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.

Topics: Adolescent; Adult; Aged; beta 2-Microglobulin; Chemotaxis, Leukocyte; Female; Foot Dermatoses; Hand Dermatoses; Humans; Lactoferrin; Male; Middle Aged; Muramidase; Neutrophils; Phagocytosis; Psoriasis; Suppuration

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.

Topics: Cathepsin G; Cathepsins; Cytoplasmic Granules; Endopeptidases; Humans; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Psoriasis; Serine Endopeptidases; Time Factors

Previous studies have demonstrated alterations in polymorphonuclear leukocyte (PMNL) function in patients with psoriasis, but results have been variable. In this study we attempted to determine whether functional changes in PMNL from psoriatics represented an intrinsic cellular defect or a response to factors in serum. We evaluated the effect of the continuous presence of autologous and heterologous serum on lysozyme release and superoxide anion (O2-) generation by psoriatic and normal PMNL exposed to a soluble or particulate phagocytic stimulus. There were no differences in O2- generation or lysozyme release between normal and psoriatic PMNL without serum. However, in the presence of 10% autologous serum, these responses were significantly decreased for psoriatic PMNL (p less than .001). The results were not time-dependent and did not correlate with the extent of psoriatic involvement. The data support the hypothesis that serum factors exist in patients with psoriasis that may affect PMNL functions. The presence or absence of such factors could explain, in part, the differences between the various investigations of PMNL function in psoriasis.

Topics: Cytochrome c Group; Granulocytes; Humans; Muramidase; Phagocytosis; Psoriasis; Superoxides

A total of 28 psoriatics and the same number of healthy individuals as controls were subjected to chemical analyses of their lacrimal fluid and parotid saliva to assess whether any functional disturbances attributable to psoriasis were detectable, i.e. if they have sicca syndrome (SS) or not. The stimulated parotid flow rate and Schirmer test I proved to be normal in both series. A significant elevation of salivary IgA, alpha-amylase, and Na+ was found in psoriatics when compared with the controls. On the other hand, salivary lysozyme values in psoriatics were markedly lowered. There was a distinct interrelationship between salivary IgA, beta 2-microglobulin, and lysozyme detectable in both series. The findings are discussed in terms of the increased immunological activity in psoriasis, and the possible role of cAMP and neural regulation in the causation of elevated amylase and Na+ levels in psoriatics is hypothesized. These alterations in salivary constituents might provide a protective system for oral mucous membranes against this skin disease.

Topics: Adult; alpha-Amylases; beta 2-Microglobulin; Female; Humans; Immunoglobulin A; Male; Middle Aged; Muramidase; Parotid Gland; Psoriasis; Saliva; Sodium; Tears

Vitamin A (retinol) and its analogues (retinoids) are clinically effective in cystic acne and psoriasis, diseases in which neutrophils may constitute major components of inflammatory cell infiltrates. We found that the earliest histopathologic alteration in psoriasis is the disappearance of neutrophils at 2 to 4 weeks after the initiation of therapy with etretinate. Since retinoids may exert anti-inflammatory effects by virtue of an action upon neutrophils, we studied the effects of the following retinoids on discrete neutrophil functions in vitro: retinol, retinyl acetate, retinal, tretinoin, isotretinoin, etretinate, and Ro 10-1670. Although they had no significant effects upon aggregation, chemokinesis, or chemotaxis, all of the retinoids, with the exception of etretinate and Ro 10-1670, profoundly inhibited superoxide anion production and lysosomal enzyme release. Tretinoin and isotretinoin were the most effective inhibitors. We propose that these drugs exert their pharmacologic effects (resolution of inflammatory lesions) by inhibiting the release of mediators of inflammation and by preventing the accumulation of neutrophils in acne lesions when applied topically or systemically, respectively.

Topics: Cell Aggregation; Chemotaxis, Leukocyte; Glucuronidase; Humans; In Vitro Techniques; Muramidase; Neutrophils; Psoriasis; Superoxides; Vitamin A

Topics: Adolescent; Adult; Baths; Complement System Proteins; Female; Humans; Immunoglobulins; Male; Middle Aged; Muramidase; Psoriasis

Topics: Adult; Complement System Proteins; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Middle Aged; Muramidase; Properdin; Psoriasis; Time Factors

Topics: Adult; Antibodies; Female; Humans; Male; Middle Aged; Muramidase; Psoriasis; Remission, Spontaneous