PubMed Health⌕ Search

Biomedical subjects

Stephan Grabbe

Publications and source records attributed to Stephan Grabbe.

5 recordsLinked to original sources
PubMed2003

Significant risk of a second melanoma in patients with a history of melanoma but no further predisposing factors.

It is a well-accepted fact that melanoma patients are prone to develop further melanomas. In a cohort of 535 melanoma patients, we determined the incidence of second melanomas, as well as risk factors known to be associated with melanoma development. A retrospective analysis of patients regularly consulting our melanoma care unit revealed second or even further melanomas in 5.6% (n = 30). When compared to the overall population, melanoma patients have at least a 30-fold increased risk for the development of a second melanoma. Twenty of these 30 patients revealed none of the known predisposing conditions for multiple melanomas.

Female↗
PubMed2003

Monocyte and macrophage functions in M-CSF-deficient op/op mice during experimental leishmaniasis.

Mice with a naturally occurring Csfm(op)/Csfm(op) (op/op) gene mutation lack functional macrophage-colony stimulating factor (M-CSF) and are deficient of M-CSF-derived macrophages. They are severely monocytopenic, and their remaining M-CSF-independent macrophages were shown to differ in differentiation and distinct functions when compared with phenotypically normal mice of the same background. It is not known if osteopetrosis mice (op/op mice) are able to mount a specific immune response against intracellular pathogens, as this would require complex effector functions by macrophages. We therefore investigated the ability of op/op mice and their M-CSF-independent macrophages to combat infection with Leishmania major. op/op mice retained the ability to resist an infection with L. major by mounting a T helper cell type 1 cell response, eliminating parasites and resolving the lesions. Macrophages from op/op mice were able to sufficiently perform effector functions in vitro, such as phagocytosis, production of leishmanicidal nitric oxide (NO), killing of parasites, and release of interleukin (IL)-12. There were quantitative differences, as M-CSF-derived macrophages from hematopoietic organs of control mice showed significantly higher rates of phagocytosis and higher NO release after stimulation with lipopolysaccharides than corresponding macrophages from op/op mice. In contrast, when peritoneally elicited macrophages were used, those from op/op mice revealed a stronger response than those from control mice with regard to release of NO or IL-12. These differences suggest that M-CSF-independent maturation of op/op monocytes subsequent to their release from hematopoietic tissue exerts influence on their effector functions. However, M-CSF or M-CSF-derived macrophages are not necessary for an effective immune response against L. major.

Animals↗
PubMed2002

Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1.

Inflammatory processes are associated with the rapid migration of dendritic cells (DCs) to regional lymph nodes and depletion of these potent antigen-presenting cells (APCs) from the inflamed tissue. This study examined whether sites of cutaneous inflammation can be repopulated with DCs from a pool of immature DCs circulating in the blood. In adoptive transfer experiments with ex vivo-generated radioactively labeled primary bone marrow-derived DCs injected into mice challenged by an allergic contact dermatitis reaction, immature DCs were actively recruited from the blood to sites of cutaneous inflammation, whereas mature DCs were not. Immature, but not mature, DCs were able to adhere specifically to immobilized recombinant E- and P-selectin under static as well as under flow conditions. P-selectin-dependent adhesion of immature DCs correlates with their higher level of expression of the carbohydrate epitope cutaneous lymphocyte-associated antigen (CLA) and is blocked by a novel inhibitory antibody against mouse P-selectin glycoprotein ligand 1 (PSGL-1). Surprisingly, however, emigration of immature DCs into inflamed skin is retained in the presence of this anti-PSGL-1 antibody and is also normal when immature DCs are generated from fucosyltransferase (Fuc-T) Fuc-TVII-deficient mice. By contrast, emigration of wild-type immature DCs is reduced by adhesion-blocking anti-E- and P-selectin antibodies, and immature DCs generated ex vivo from Fuc-TVII/Fuc-TIV double-deficient mice emigrate poorly. Thus, fucosylated ligands of the endothelial selectins, determined in part by Fuc-TIV, and independent of PSGL-1, are required for extravasation of DCs into sites of cutaneous inflammation.

Animals↗
PubMed2002

Beta2 integrins are required for skin homing of primed T cells but not for priming naive T cells.

Beta2 integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of beta2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta2 integrin subunit, CD18. ACD and DTH responses, but not edema formation, were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-) mice. CD18(-/-)lymph nodes (LNs) contained an abnormal population of CD3(-)CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.

Animals↗