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Biomedical subjects

F Valentine

Publications and source records attributed to F Valentine.

24 records · Page 2Linked to original sources

Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome.

We investigated the possible role of a defect in antigen-presenting cells in the acquired immunodeficiency syndrome (AIDS), by enumeration of Langerhans' cells, the epidermal antigen-presenting cells. These cells were stained for the characteristic markers, surface Ia antigen and surface ATPase activity. A significant reduction was observed in the number of stained cells per square millimeter of body-surface area in 24 patients with AIDS and either opportunistic infections (Ia, 258 +/- 34, and ATPase, 274 +/- 46) or Kaposi's sarcoma (Ia, 378 +/- 100, and ATPase, 530 +/- 26), as compared with 38 appropriate controls (Ia, 721 +/- 13, and ATPase, 693 +/- 12). Examination of six patients with an "AIDS-related complex" revealed significantly reduced numbers of Langerhans' cells per square millimeter; this reduction was more pronounced in staining for Ia antigen (306 +/- 69) than in staining for ATPase activity (517 +/- 101). Given the known role of Ia expression in antigen presentation, we suggest that functional alterations in Langerhans' cells, and perhaps also in antigen-presenting cells in tissues other than skin, may be involved in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗

Cytotoxicity of natural killer cells: correlation with emperipolesis and surface enzymes.

Cell-mediated cytotoxicity involving natural killer cells requires contact between effector and target cells for effective cytolysis. Ultrastructural studies of biopsies of primary human malignant melanoma showed mononuclear leukocytes to be located in close proximity to tumor cells and, on occasion, within the confines of the melanoma cell itself. This phenomenon, called emperipolesis, was examined in vitro to determine whether the same population of cells that exhibits emperipolesis is responsible for cytotoxicity. Since natural killer cells have been identified morphologically and functionally as large granular lymphocytes with surface receptors for the Fc portion of immunoglobulin (FcR+ cells), lymphocytes were depleted of FcR+ cells, and their cytotoxicity and ability to emperipolese were measured. Both of these properties were markedly diminished (88 and 85 per cent, respectively). Systematic comparison of emperipolesis and cytotoxicity from donors known to exhibit either high or low lymphocyte cytotoxicity showed perfect concordance. Ultrastructural analysis of in vitro emperipolesis revealed the emperipolesing lymphocytes to be FcR+ cells establishing identity with the large granular cells known to mediate cytotoxicity. The morphologic marker found in both FcR+ cells, purified by rosetting techniques, and in emperipolesed lymphocytes consisted of cytoplasmic parallel tubular arrays. Further studies designed to elucidate a mechanism for cytotoxicity and emperipolesis implicated cell surface proteases as mediators of these activities. Competitive inhibition of surface proteases with artificial and natural inhibitors markedly reduced both cytotoxicity and emperipolesis. Therefore, it is likely that lymphocytes that are FcR+ participate in cell-medicated cytotoxicity through mechanisms involving cell contact and enzyme-initiated damage of target cells. Emperipolesis represents one type of effector-target cell contact leading to cytotoxicity.

Adult↗

Interaction of mononuclear leukocytes with malignant melanoma.

Since it is well established that cellular immunity plays a role in the defense against melanoma, the morphologic aspects of this reaction warranted investigation. Accordingly, peripheral blood mononuclear cells obtained from healthy donors were incubated with human melanoma cells for 1 to 24 hours to examine, on the ultrastructural level, the cellular interaction that eventuates in cytolysis of the tumor cells. Within 1 hour of incubation, monocytes and lymphocytes were seen attached to approximately 40 per cent of the melanoma cells with marked interdigitation of cellular processes. After 4 hours of incubation, the percentage of tumor cells with attached leukocytes remained the same, but 2 to 9 per cent of the melanoma cells showed interiorized lymphocytes when kept in suspension, 10 to 25 per cent when maintained in culture dishes. Erythrocytes or fixed lymphocytes were not taken up by the melanoma cells nor were living lymphocytes seen in fibroblasts or endothelial cells which served as controls for the neoplastic cell lines. Thus, melanoma cells did not prove to be randomly phagocytic, and the interiorization displayed by lymphocytes--a process called emperipolesis--appears to be selective. It is postulated that emperipolesis may enhance the tumoricidal effect exerted by cytotoxic lymphocytes on melanoma cells.

Cell Adhesion↗