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Biomedical subjects

M G Tonnesen

Publications and source records attributed to M G Tonnesen.

27 records · Page 2Linked to original sources
PubMed1984

Neutrophil-endothelial cell interactions. Modulation of neutrophil adhesiveness induced by complement fragments C5a and C5a des arg and formyl-methionyl-leucyl-phenylalanine in vitro.

Neutrophil adherence to vascular endothelial cells is the initial event in the emigration of neutrophils through blood vessel walls to tissue sites of inflammation; this process is attributed to the generation of extravascular chemotactic factors. To investigate the effect of chemotactic factors on neutrophil adherence to endothelium, we developed a sensitive, reproducible in vitro microtiter adherence assay. Base-line nonstimulated adhesion of human neutrophils to cultured human umbilical vein endothelial cell monolayers was 35.2 +/- 0.9%, which is equivalent to three to four neutrophils per endothelial cell. Addition of either purified complement fragment C5a des arg, or formyl-methionyl-leucyl-phenylalanine (FMLP), in concentrations ranging from 10(-10) to 10(-6) M, increased neutrophil adherence to endothelium in a dose-dependent manner. Purified C5a and C5a des arg were essentially equal in their ability to enhance neutrophil adherence, in contrast to the previously described greater in vitro potency of C5a compared with C5a des arg in stimulating neutrophil chemotaxis and enzyme release. Nonstimulated neutrophils adhered preferentially to human endothelial cells compared with fibroblasts or smooth muscle cells, suggesting that endothelial cells may make a unique contribution to the base-line adhesive interaction. However, chemotactic factors appear to enhance neutrophil adherence to endothelium by exerting an effect primarily on the neutrophil. In the presence of chemotactic factor, neutrophils adhered equally well to different cell types or to protein-coated plastic. Pretreatment of endothelial cells with chemotactic factor for as long as 4 h failed to increase subsequent neutrophil adherence. In contrast, pretreatment of neutrophils with chemotactic factor increased adherence to endothelium. Chemotactic factor-stimulated neutrophil adherence to endothelium occurred rapidly (within 2 min), diminished upon removal of stimulus, but could be rapidly and maximally restimulated upon readdition of the original dose of chemotactic factor. Thus, adherence to endothelium stimulated by chemotactic factor would appear to be a dynamic neutrophil response capable of rapid modulation, possibly important to the ability of neutrophils to adhere to and then migrate through vessel walls to localize at sites of inflammation.

Animals↗
PubMed1984

Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme.

The commonest variety of erythema multiforme follows a lesion caused by a recurrent herpes simplex virus infection. In studying the immunopathogenesis of herpes-associated erythema multiforme, we examined skin lesions for the presence of a herpes simplex viral antigen by an indirect immunofluorescence test using a monoclonal antibody to a major type-common glycoprotein antigen, gB. Focal staining showed this antigen to be present in epidermal cells in 12 of 16 skin biopsy specimens. The staining was similar to, but less intense than, that seen in biopsy samples of lesions of recurrent herpes simplex virus infections. Similar findings were not seen in control skin biopsy specimens from lesions of other skin diseases; a control monoclonal stain also was negative in biopsy specimens. These findings suggest that the immune reaction and subsequent tissue damage of herpes-associated erythema multiforme are due to the presence of herpes antigens in the skin.

Antibodies, Monoclonal↗
PubMed1983

Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes.

Erythema multiforme (EM), in its modern definition, is an acute, self-limited syndrome with distinctive skin lesions with or without mucosal lesions. Use of the terminology "EM minor" and "EM major" is a reasonable approach to separating the classical mild cutaneous syndrome, as described by Hebra (EM minor), from the usually more severe syndrome, with marked mucosal damage, as described by Stevens and Johnson (EM major). Until objective markers for EM are available, we propose preliminary diagnostic criteria for EM, based primarily on clinical features. Although hundreds of factors have been reported to cause EM, only a limited number are reasonably well documented as possible precipitating agents. Recurrent herpes simplex is an important etiologic factor in EM minor, while mycoplasmal infections and drugs may be associated with EM major. Progress in the understanding of EM will require careful attention to definition and diagnostic criteria and identification of distinct clinical and etiologic subsets within the spectrum of EM.

Erythema Multiforme↗
PubMed1983

Lymphocyte subsets and Langerhans cells/indeterminate cells in erythema multiforme.

A peroxidase-antiperoxidase study using monoclonal antibodies directed against T and B lymphocytes and Langerhans cells/indeterminate cells (LC/IC) was undertaken in order to understand more clearly the changes observed in erythema multiforme. At the various stages of development, from normal skin to target lesions, the quantity of inflammatory cells differed, but in each case the number of T8+ (cytotoxic/suppressor) cells was greater than the number of T4+ (helper/inducer) cells in the epidermis, whereas the latter exceeded the former in the dermis. Concomitant with the initial epidermis changes, there was an increase in the number of T6+ (LC/IC) cells in the upper and lower epidermis. With slight to moderate basal unit destruction, the number of LC/IC in the upper epidermis exceeded those in the lower epidermis. With severe basal unit destruction, there was a loss of LC/IC in the lower epidermis as detected by T6 reactivity. In fully formed blisters, the LC/IC in the upper half of the epidermis were decreased in parallel with the degree of epidermal necrosis. The character of the lymphocytic inflammatory infiltrate and redistribution in LC/IC are similar to those findings described in allergic contact dermatitis. The clinical, histologic, and immunopathologic changes in erythema multiforme appear to be due in part to cellular immune mechanisms with the lymphocyte as the predominant effector cell, and our data suggest a possible role for LC/IC in this disorder.

Erythema Multiforme↗
PubMed1983

Erythema multiforme: microvascular damage and infiltration of lymphocytes and basophils.

The sequence of alterations occurring in recurrent erythema multiforme was studied with clinical observations, 1-micrometer tissue sections, and immunofluorescence techniques. Lesions evolved through 3 stages: an initial red papule, a vesicle surmounting a red papule, and a target (iris) lesion. Focal endothelial cell swelling was present in clinically normal skin. In the red papule, endothelial cytoplasmic swelling, vacuolization, and nuclear hypertrophy with luminal obliteration of superficial venules developed. These venular alterations were more marked with endothelial cell necrosis, and involved deeper venules as well in vesicular and target lesions. Lymphocytes surrounded the venules and infiltrated the lower epidermis in the red papule and the vesicular lesions. Venular damage was correlated with the degree of infiltration by lymphocytes, apparently the primary effector cell, suggesting the venule as a primary target of injury. Hypogranulated basophils were noted around venules in vesicular and target lesions. Fibrin deposits were identified within and interstitially beneath the vesicles. The presence of lymphocytes, basophils, and interstitial fibrin deposition is similar to the changes of cutaneous delayed-type hypersensitivity and suggests a role for cell-mediated immunity in the pathogenesis of erythema multiforme.

Adolescent↗
PubMed1982

Identification of a human neutrophil angiotension II-generating protease as cathepsin G.

A human neutrophil protease, initially termed neutral peptide-generating protease, has been shown to cleave angiotensin II directly from angiotensinogen and has been identified as leukocyte cathepsin G. When purified neutrophils were disrupted by nitrogen cavitation and fractionated by differential centrifugation, 44 and 24% of the angiotensin II-generating activity was in the lysosomal and undisrupted cell fractions, respectively. Cytochalasin B-treated human neutrophils stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine released beta-glucuronidase, lysozyme, and angiotensin II-generating protease in a dose-dependent fashion, consistent with localization of this protease to the neutrophil granule. Individually purified angiotensin II-generating protease and cathepsin G had similar proteolytic and esterolytic activity for angiotensinogen and N-benzoyl-L-tyrosine ethyl ester on a weight basis, exhibited identical mobilities by SDS-gradient polyacrylamide gel electrophoresis and pH 4.3 disc-gel electrophoresis, and gave precipitin lines of antigenic identity on Ouchterlony analysis with goat antibody to the angiotensin II-generating protease. Thus, the angiotensin II-generating protease of human neutrophils has been identified as cathepsin G on the basis of subcellular localization, substrate specificity, physicochemical characteristics, and antigenic identity.

Angiotensin II↗
PubMed1982

The microvasculature in inflammation.

During inflammation, neutrophils migrate out of blood vessels into the surrounding tissues. A number of studies in vivo have indicated that chemotactic factors, particularly fragments derived from the fifth component of complement, are able to mediate this emigration. The ability of C5 fragments to induce migration of neutrophils through the endothelium and internal elastic lamina of the rabbit carotid artery in vivo was investigated. Application of C5 fragments to the adventitial surface of the artery, in combination with either mechanical trauma or the simultaneous administration of PGE2, resulted in neutrophil adherence to the endothelium and migration into the vessel wall. The demonstrated ability of neutrophils to interact with the endothelial cells of large arteries validates to some extent the use of readily available large vessel endothelium for the in vitro examination of neutrophil-endothelial cell adherence, the initial step in the process of emigration. A sensitive, reproducible assay has been established which allows the assessment of neutrophil adherence to human umbilical vein endothelial cell monolayers. Adherence could be stimulated in vitro in a dose-response fashion by the addition of chemotactic factors, either fMetLeuPhe or C5 fragments. The synergistic effect of PGE2 observed in the in vivo transmigration system was not apparent in the in vitro adherence assay. It is possible that PGE2 does not participate at the level of the initial neutrophil-endothelial adhesive interaction. Pretreatment of the endothelium with the chemotactic factors failed to induce increased adherence and may suggest that the effect of chemotactic factors on adherence is primarily, if not entirely, limited to the neutrophil.

Animals↗
PubMed1979

Erythema multiforme.

Erythema multiforme (EM) is an episodic, variable, self-limited, and often recurrent inflammatory disorder of the skin and mucous membranes. In this article a definition of EM is proposed, its known clinical and histopathologic spectrum is reviewed, an approach to diagnosis and treatment is suggested, and documented evidence regarding its etiology and pathogenesis is presented. EM would appear to be a hypersensitivity reaction to a variety of precipitating agents. It has been directly linked to Mycoplasma pneumoniae and herpes simplex virus infections and possibly is triggered by a number of other infectious agents and by certain drugs. Accumulating observations of diverse immunologic phenomena suggest an underlying immune mechanism of as yet unclear type. Future investigation should be directed toward defining diagnostic criteria, evaluating reported etiologic associations, and clarifying the immunologic basis of this complex and enigmatic disorder.

Diagnosis, Differential↗