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Biomedical subjects

F A Kaplan

Publications and source records attributed to F A Kaplan.

5 recordsLinked to original sources
PubMed1998

Cell surface expression of a human IgG Fc chimera activates macrophages through Fc receptors.

Antibody-dependent cell-mediated cytotoxicity plays an important role in the macrophage-mediated destruction of target cells. While the selectivity is based on antibody specificity, the lytic attack is triggered by Fc receptor-mediated respiratory burst. To mimic IgG opsonization, a chimeric antibody-like molecule, containing human IgG1 Fc, was expressed on the surface of mammalian cells. The transmembrane domain of the human transferrin receptor was fused in-frame to the N-terminus of the second and third domains of human IgG1 heavy-chain constant region. This fusion molecule was designed to take advantage of the type II membrane anchor property of the transferrin receptor to express the Fc portion of the molecule in a reverse orientation, such that the Fc portion projected away from the cell surface. This is in contrast to the conventional cell surface IgG, which is anchored by a C-terminal type I transmembrane domain. The cell surface expressed reverse Fc no longer activated complement, but retained Fc receptor-binding capability and activated superoxide production by macrophages. This activity was completely blocked by an FcgammaR I-specific monoclonal antibody.

Animals↗
PubMed1996

Peripheral xenogeneic immunological response to encapsulated bovine adrenal chromaffin cells implanted within the sheep lumbar intrathecal space.

Bovine adrenal chromaffin (BAC) cells were encapsulated in polymer membranes and placed into the lumbar intrathecal (subarachnoid) space of sheep for up to 12 weeks in the absence of immunosuppression. Humoral and cellular immunological responses in the sheep were evaluated over this time course using the following assays: (1) serum-dependent cytotoxic antibody determinations, (2) flow cytometric sheep anti-bovine IgM and sheep antibovine IgG antibody analysis, (3) alterations in cellular immune markers, and (4) T cell responsiveness of the host using one-way mixed lymphocyte reactions. Complement-dependent cytotoxic antibody testing demonstrated that none of the sheep implanted with the encapsulated BAC cells were sensitized to antigens from transplanted cells in the device. There were no alterations of cellular immune markers in the blood of the transplanted sheep and no positive T cell responses were elicited by exposure of unprimed or primed in vivo host lymphocytes to unencapsulated BAC cells in vitro. Morphological analysis of the explanted devices demonstrated that all capsules contained viable cells and 20 of 21 devices released basal and nicotine-stimulated norepinephrine as determined by HPLC analysis. These observations suggest that an encapsulating membrane can provide an immunoisolatory barrier enabling successful xenogeneic transplantation.

Adrenal Medulla↗
PubMed1993

"Neutral allografts"--lack of allogeneic stimulation by cultured human cells expressing MHC class I and class II antigens.

Cultured human dermal fibroblasts, smooth muscle cells, epidermal cells and endothelial cells were tested for immunogenicity in an in vitro allostimulation assay. Gamma interferon was used to induce MHC class II expression, since these cells constitutively express class I but not class II antigens. In contrast to human dermal fibroblasts, smooth muscle cells and epidermal cells, endothelial cells, were able to stimulate a significant proliferative response in normal allogeneic lymphocytes. Since ICAM-1 was also expressed on these cells, this inability to initiate allostimulation was probably not due to the absence of adhesion molecules. Addition of exogenous cytokines such as IL-1, IL-2, and TNF did not restore T cell proliferation in the test system. Therefore the inability of dermal fibroblasts, smooth muscle cells, and epidermal cells to initiate significant allostimulation was also not due to lack of cytokine production. It appears that certain cells lack as-yet-undefined costimulatory factors required for their effective recognition as foreign. These results support the notion that cultured human fibroblasts, smooth muscle cells, and epidermal cells could serve as building blocks of engineered "neutral allografts" for use across MHC barriers.

Antigenic Modulation↗
PubMedDate not supplied

Two PC12 pheochromocytoma lines sealed in hollow fiber-based capsules tonically release L-dopa in vitro.

Two PC12 cell-derived lines have been studied following encapsulation into polymer-based hollow fibers with respect to secreted catecholamines and their metabolites. Cellular encapsulation provides a chronic microperfusion environment within which basally secreted PC12 products can be readily measured. Encapsulated PC12 cells grown and held under the conditions specified in this report basally release amounts exceeding their total cellular stores of the dopamine precursor L-DOPA and the electrochemically active dopamine metabolites DOPAC and HVA during 45-min static incubations. Under these same conditions, these cells release less than 0.1% of their total cellular store of dopamine. Depolarizing incubations enhance dopamine secretion eightyfold and enhance secretion of L-DOPA, HVA, and DOPAC about twofold. The relative composition of products basally secreted differs between PC12-derived cell lines, and an inverse relationship exists between basal release of L-DOPA and total cellular store of dopamine. These results further indicate that selected PC12 cell lines are potentially a source of both dopamine and L-DOPA in therapeutic cellular replacement applications.

3,4-Dihydroxyphenylacetic Acid↗