Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy.

Background: The clinical relevance of gastrointestinal food allergy in adults is largely unknown because the mechanisms are poorly understood and the diagnosis is difficult to confirm.

Aims: To improve the diagnostic means for confirming intestinal food allergy on an objective basis, a new colonoscopic allergen provocation (COLAP) test was developed.

Patients: The COLAP test was performed in 70 adult patients with abdominal symptoms suspected to be related to food allergy, and in five healthy volunteers.

Clinical significance of the colonoscopic allergen provocation test.

Background: To improve the diagnosis of intestinal allergy, we developed a colonoscopic allergen provocation (COLAP) test.

Methods: The cecal mucosa was challenged with three food antigen extracts, a buffer control and a positive control (histamine). The mucosal wheal and flare reaction was registered semiquantitatively 20 min after challenge, and selected tissue biopsies were examined for mast cell and eosinophil activation by immunohistochemistry and electron microscopy.

Mechanisms of human eosinophil activation by complement protein C5a and platelet-activating factor: similar functional responses are accompanied by different morphologic alterations.

The complement system is an important amplification system for the propagation of allergic as well as pseudoallergic inflammatory reactions. In the present study, the effect of the major anaphylatoxin C5a was compared with that of platelet-activating factor (PAF) on highly purified eosinophils (> or = 95%) by functional as well as morphologic criteria. Upon stimulation with C5a, eosinophils maintained their spheric structure, developing short, pseudopodia-like protrusions, whereas PAF induced the generation of a number of digitating protrusions.

TNF alpha-induced activation of eosinophil oxidative metabolism and morphology--comparison with IL-5.

Human dermal mast cells are capable of releasing cytokines, particularly preformed TNF alpha, upon appropriate stimulation. Mast cell activation in vivo was shown to be associated with an influx and activation of inflammatory cells, initially PMN (polymorphonuclear neutrophilic granulocytes) then eosinophils. In order to learn more about the mechanisms by which TNF alpha is capable of activating eosinophils, in the present study the effect of TNF alpha on morphology and function of highly purified normal eosinophils (> or = 95%) was examined.

[Cell biology and function of eosinophilic granulocytes in immunologic inflammation].

In recent years, increasing evidence has accumulated to suggest that the eosinophil represents a potent cytotoxic effector cell which plays a key role in the pathogenesis of pulmonary diseases as well as other human disorders. Beside contributing to antiparasitic host defense, eosinophils can prove detrimental to a number of host organs and tissues via release of their preformed basic proteins as well as de novo generated lipid mediators or oxygen radicals. Eosinophil effector functions are stimulated by certain lipid mediators and cytokines released by other cells in the course of active disease.

The chemokine RANTES is more than a chemoattractant: characterization of its effect on human eosinophil oxidative metabolism and morphology in comparison with IL-5 and GM-CSF.

Eosinophils were shown to play a major role in the allergic inflammatory process leading to the clinical symptoms of atopic dermatitis. Only selected cytokines are capable of inducing a chemotactic response in eosinophils. In particular, the chemokine RANTES was recently shown to be a potent eosinophil chemotaxin.

Interleukin-5-induced granulocyte activation in atopic patients.

The effect of recombinant human and murine interleukin-5 (IL-5) on granulocytes was investigated in patients with atopic dermatitis (AD) and allergic rhinitis and compared with those from patients with plaque psoriasis and normal non-atopic controls. Granulocyte activation was measured as lucigenin-dependent chemiluminescence (CL) and release of eosinophil cationic protein (ECP) as well as by scanning- and transmission-electron microscopy (EM) and the ultrastructural detection of production of H2O2. A significant direct effect of both human and murine IL-5 on granulocyte oxidative metabolism could only be detected in those patients with AD and allergic rhinitis.

Humate-induced activation of human granulocytes.

Naturally occurring humic substances are particular chemical compounds which are found in humus. They bind to carbohydrates, amino acids and steroids by means of hydrogen bonds, covalent bonds and epsilon donor-acceptor complexes. Three specimens of low-molecular humic substances were tested (two naturally occurring humates and one synthetically prepared humate).

Effect of Ca-panthotenate on human granulocyte oxidative metabolism.

Activated granulocytes play an important role in propagation of the inflammatory response by production of reactive oxygen species and release of their granule content. Hyperactivation of these cells is suggested to result in deterioration of wound healing and, probably, increase of cicatrization. Pantothenic acid and its stable salt form, Ca-Panthotenate, were shown to significantly improve surgical wound healing.

Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines.

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria.

Interaction of granulocytes and endothelial cells upon stimulation with tumor necrosis factor-alpha: an ultrastructural study.

By the production of microbicidal agents, such as reactive oxygen species, activated PMN are capable of inducing tissue damage in the host. TNF-alpha was recently shown to be a potent activator of PMN oxidative metabolism. To further evaluate the interaction between activated PMN with physiological target cells, the effect of human PMN on cultured bovine aortic and human umbilical vein endothelial cells (EC) upon stimulation with human TNF-alpha was investigated by ultrastructural techniques: Scanning and transmission electron microscopy (SEM and TEM resp.

Activation of human polymorphonuclear neutrophilic granulocytes by immuno-modulating cytokines: an ultrastructural study.

Activated granulocytes play an important role in the propagation of inflammatory reactions and are capable of mediating tissue damage by the release of reactive oxygen species and lysosomal contents. Cytokines produced by immunocompetent and other cells were recently suggested to influence granulocyte functions. Therefore, in the present study, we investigated the effect of relevant immuno-modulating cytokines on isolated human granulocytes by ultrastructural criteria: scanning and transmission electron microscopy, ultrastructural detection of H2O2.

Human tumor necrosis factor is a potent activator of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: comparison with human lymphotoxin.

Besides their cytotoxic effects, Tumor necrosis factor (TNF) and Lymphotoxin (LT) were shown to modulate distinct PMN functions. Therefore, in the present study we evaluated the effect of recombinant human TNF and LT on the oxidative metabolism of isolated human PMN. In addition ultrastructural changes upon stimulation were evaluated.

Human granulocyte-macrophage colony stimulating factor: an effective direct activator of human polymorphonuclear neutrophilic granulocytes.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated.

Granulocyte-activating mediators (GRAM): III. Further functional characterization of monocyte-derived GRAM.

As shown previously monocytes upon stimulation with bacterial lipopolysaccharides (LPS) release granulocyte-activating mediator(s) (M-GRAM) which induced a long-lasting chemiluminescence (CL) response in human granulocytes. M-GRAM could be separated from interleukin-1 alpha and beta, interleukin-2, interferon alpha and gamma, granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), since these cytokines are shown to be unable to induce a significant CL response. In contrast, granulocyte macrophage colony stimulating factor (GM-CSF) and particularly tumor necrosis factor (TNF) are important triggers of the oxidative burst and they are capable of inducing a CL response.