Biomedical subjects

B I Coble

Publications and source records attributed to B I Coble.

8 recordsLinked to original sources

PubMed1999

Expression and function of beta 2 integrin CD11B/CD18 on leukocytes from patients with psoriasis.

The expression of beta 2 integrin CD11b on granulocytes and monocytes from patients with psoriasis vulgaris and pustular psoriasis was examined by flow cytometry. The amount of CD11b expressed on both granulocytes and monocytes was greater in 4 patients with pustular psoriasis than in 16 patients with psoriasis vulgaris. Its expression correlated with the development of pustules on the skin. No difference was seen between healthy blood donors and patients with active psoriasis vulgaris. Three patients with pustular psoriasis were followed during retinoid treatment. Granulocytes and monocytes showed a decrease in CD11b expression after administration of retinoids, in parallel with clearing of the skin. The adherence of granulocytes isolated from psoriasis patients was tested on cultured human umbilical vein endothelium. No significant difference in adherence was observed between control cells and cells from patients with active psoriasis vulgaris. These data indicate that the development of microabscesses in the dermis in psoriasis vulgaris is not related to enhanced beta 2 integrin function. The increased CD11b expression found in patients with pustular psoriasis may, however, serve as a triggering factor for pustule formation in pustular psoriasis.

Aged↗

PubMed1996

Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin.

Retinoids are biologic response modifiers that are present in normal skin and may possibly be perturbed in carcinogenesis. To examine this possibility in human skin, we analyzed vitamin A and cytosolic retinoid binding proteins (cellular retinol binding protein and cellular retinoic acid binding protein [CRABP]) in a total of 38 non-melanoma skin tumors and 25 healthy skin samples using high performance liquid chromatography, radioligand electrophoresis, and reverse transcriptase-polymerase chain reaction. The mean +/- SEM retinol concentration was normal in basal cell carcinoma (0.60 +/- 0.10 microM) and seborrheic keratosis (0.47 +/- 0.07 microM), but increased in keratoacanthoma (1.60 +/- 0.41 microM) and squamous cell carcinoma (1.17 +/- 0.28 microM) (p < 0.05 for both). Also, the concentrations of 3,4-didehydroretinol, a major vitamin A metabolite produced in human skin, were markedly elevated (6-7 times normal) in keratoacanthoma and squamous cell cancer. All types of tumors showed moderately increased levels of cellular retinol binding protein. In addition, keratoacanthoma and squamous cell cancer showed markedly increased levels (6-7 times normal) of CRABPII protein. Transcriptional activity of the CRABPII gene was demonstrated in both normal and neoplastic epidermis, but clear CRABPI mRNA expression was found only in basal cell carcinoma. The data indicate that characteristic perturbations of the vitamin A and retinoid binding protein levels occur in squamous cell-derived skin tumors, but whether these reflect intrinsic errors in retinoid metabolism or are secondary to abnormal cellular differentiation is unknown.

Aged↗

PubMed1988

Function of exudate neutrophils from skin in psoriasis.

Human neutrophils harvested from skin chambers containing autologous serum in psoriatic patients were compared with peripheral blood neutrophils by examining migration, phagocytosis, and oxidative activation. Random migration was reduced in exudate cells, whereas the chemotactic response to yeast-activated serum was evident not only in blood neutrophils, but also in exudate cells. The metabolic activation of exudate neutrophils, when stimulated with formyl-methionyl-leucyl-phenylalanine and measured as chemiluminescence, was enhanced by 50-400% compared to blood neutrophils. The chemiluminescence response to phorbol myristate acetate was on the other hand reduced to 35%. In the phagocytic assay, using C3bi- and IgG-opsonized yeast particles, exudate neutrophils from non-psoriatic healthy controls showed enhanced uptake of C3bi-coated yeast compared to blood neutrophils. In psoriatics, the blood neutrophils showed enhanced C3bi-mediated phagocytosis compared to non-psoriatic control cells. No further increase in C3bi-mediated phagocytosis was then seen in exudate cells from these patients. IgG-mediated phagocytosis was in contrast to C3bi similar between blood and exudate neutrophils in psoriatics and non-psoriatic controls. These experiments show that during exudation priming of different receptor-mediated processes can occur. However, no significant difference was observed between different functional capacities in exudate neutrophils from psoriasis patients and non-psoriatic controls.

Adult↗

PubMed1987

Neutrophil function in psoriasis: effects of retinoids.

The present investigation focused on the oxidative response of polymorphonuclear neutrophil leukocytes in psoriasis, in particular pustular psoriasis and how this response was affected by different retinoid compounds. In the active phase of pustular psoriasis, the neutrophil chemiluminescence response to the chemotactic peptide f-met-leu-phe and to phorbol myristate acetate was enhanced and correlated to the development of pustules, whereas cells from psoriasis vulgaris patients showed normal chemiluminescence response. Retinoids, particularly tretinoin (= retinoic acid) and isotretinoin caused a pronounced inhibition of the chemiluminescence response only in primed neutrophils in vivo and in vitro, whereas etretinate and the metabolite Ro 10-1670 was less inhibitory. Retinoic acid furthermore inhibited the Fc-mediated phagocytosis, but did not affect C3bi-mediated phagocytosis. These data suggest that the antiinflammatory effect of retinoids may operate by affecting neutrophil activation and function.

Acitretin↗

PubMed1984

Myeloperoxidase reduces the opsonizing activity of immunoglobulin G and complement component C3b.

The effect of myeloperoxidase, hydrogen peroxide (H2O2) and a halide (Cl) on the opsonizing molecules in immunoglobulin G (IgG) and complement factor C3b was assayed. At concentrations of the enzyme (1 microgram/ml) that can be found in the extracellular fluid during inflammation, the myeloperoxidase-H2O2-Cl system inhibited the opsonizing effect of IgG and C3b measured as phagocytic uptake and superoxide generation. The effect was related to the enzymatic peroxidative activity of the protein. The presence of albumin (10 mg/ml) reduced the effect of myeloperoxidase with 10-20%. Taurine, which in the presence of myeloperoxidase-H2O2-Cl forms hydrophilic chloramines, and D-penicillamine, which scavenges HOCl, neutralize the inhibitory effect of myeloperoxidase. This suggests that either hypochlorous acid or lipophilic chloramines may exert its effect by oxidizing free sulphydryl groups exposed on the opsonizing ligands. Since the myeloperoxidase-H2O2-halide system also affects chemotactic factors, leukotrienes, proteinases and membrane receptors, the system may in several ways affect the development of the inflammatory response.

Complement C3b↗

PubMed1984

Histamine release from mast cells during phagocytosis and interaction with activated neutrophils.

Histamine release from rat peritoneal mast cells was evaluated during interaction with IgG, C3b-bi and Concanavalin A-opsonized yeast particles and activated neutrophils. In contrast to others we could show no phagocytic uptake of yeast particles attaching to Fc, or Concanavalin A receptors on the mast cell. Attached yeast particles opsonized with C3b/bi were also poorly ingested (less than 10% of the attached particles.) Neither could we detect any significant histamine release. If, however, neutrophils were added to the mast cell-yeast particle complex, histamine release was induced particularly in the presence of Concanavalin A-yeast. We furthermore showed that phorbol myristate acetate-activated neutrophils and eosinophils initiated mast cell degranulation and histamine release. This release is not dependent on myeloperoxidase, but on other oxidative metabolites, since myeloperoxidase-deficient neutrophils also induce histamine release. These experiments show that mast cells exposed to immune complexes and activated neutrophils or eosinophils may augment the inflammatory response.

Eosinophils↗

PubMed1984

Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient.

Patients lacking the primary granulae enzyme, myeloperoxidase (MPO), do not usually show any increased susceptibility to infection or altered inflammatory response, in contrast to several other biochemical defects in polymorphonuclear neutrophils. We have now evaluated the role of MPO on phagocyte function in a patient with complete MPO deficiency suffering from generalized pustular psoriasis. We found that the MPO-deficient neutrophils showed enhanced phagocytosis (greater than 200% of normal) of IgG- and C3b-opsonized yeast particles and prolonged N-formylmethionyl-leucyl-phenylaline-mediated stimulation of superoxide production. When purified human MPO was added to normal neutrophils during cell adhesion, their Fc- and C3b-mediated phagocytosis was reduced without affecting cell viability. 1 microgram/ml of MPO reduced the Fc and C3b phagocytosis to 47 and 65%, respectively, whereas 10 micrograms/ml reduced the activity to 20 and 54%. Both attachment and ingestion were reduced to a similar extent, indicating that MPO affected the receptor function per se. When MPO was added to the hyperactive MPO-deficient cells, phagocytosis was reduced more rapidly. Catalase, azide, and methionine eliminated the inhibitory effect, and catalase and methionine, in fact, enhanced the phagocytic activity of adherent neutrophils. These data indicate that, apart from being a potent antimicrobial system, the oxidizing activity of the MPO-H2O2-halide system may modulate the inflammatory response by impairing certain receptor-mediated recognition mechanisms of phagocytic cells, which otherwise could elicit inflammatory reactions and tissue injury.

Complement C3b↗

PubMed1983

A quantitative microassay for leukocyte chemotaxis, using a microscopic slide system with complement-activating yeast particles as gradient source.

A simple quantitative microassay was developed for studying polymorphonuclear leukocyte (PMNL) chemotaxis under conditions where the number of available cells is a limiting factor, e.g., pustules, neutropenia, small children and cerebrospinal fluid. PMNL suspensions are placed on glass slides to which fluorescein-labeled yeast particles have been fixed. After adherence, normal human serum is added to the slides. Owing to complement activation, a chemotactic gradient which attracts the adherent PMNL is formed around the yeast particles. The number of PMNL-associated yeast particles in the presence of normal serum is scored, and compared with cells migrating in the presence of inactivated serum or in the absence of serum. A locomotory index is calculated as the number of yeast particles associated with PMNL divided by the total number of yeast particles.

Blood Physiological Phenomena↗