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S Dolich

Publications and source records attributed to S Dolich.

5 recordsLinked to original sources
PubMed1997

Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.

Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein. Full-length recombinant neurotactin is localized on the surface of transfected 293 cells. Recombinant neurotactin containing the chemokine domain is chemotactic for neutrophils both in vitro and in vivo. Neurotactin messenger RNA is predominantly expressed in normal murine brain and its protein expression in activated brain microglia is upregulated in mice with experimental autoimmune encephalomyelitis, as well as in mice treated with lipopolysaccharide. Distinct from all other chemokine genes, the neurotactin gene is localized to human chromosome 16q. Consequently we propose that neurotactin represents a new delta-chemokine family and that it may play a role in brain inflammation processes.

Animals↗
PubMed1995

High activity suppression of myeloid progenitor proliferation by chimeric mutants of interleukin 8 and platelet factor 4.

The proliferation of human myeloid progenitor cells is negatively regulated in the presence of certain members of the chemokine family of molecules. This includes interleukin 8 (IL-8) and platelet factor 4 (PF4), which in combination are able to synergize, resulting in cell suppression at very low concentrations of these molecules. A series of PF4 and IL-8 mutant proteins were analyzed in an in vitro colony formation assay for myeloid progenitor cells to assess domains of these proteins that are required for activity. Mutation of either of the two DLQ motifs within PF4 resulted in an inactive protein. Perturbations within the IL-8 dimer interface region also resulted in mutants that were incapable of suppressing colony formation. A class of chimeric mutants consisting of domains of either PF4 and IL-8, Gro-alpha and PF4, or Gro-beta and PF4 were observed to inhibit myeloid cell proliferation at concentrations which were between 500- and 5000-fold lower than either the IL-8 or PF4 wild-type proteins alone. These chimeric mutants possessed activities that were comparable to or better than the activity observed when IL-8 and PF4 were added together in vitro. One of these highly active chimeric proteins was observed to be 1000-fold more active than either IL-8 or PF4 alone in suppressing not only the proliferation but also the cell cycling of myeloid progenitor cells following intravenous injection of the mutant into mice. Examination of additional IL-8-based mutants in the colony formation assay, which centered on the perturbation of the amino-terminal "ELR" motif, resulted in the observation that the highly active IL-8 mutant required both aspartic acid at amino acid residue 4 and either glutamine or asparagine at residue 6. Single mutations at either of these positions resulted in mutants with myelosuppressive activity equivalent to wild-type IL-8. Mutants such as IL-8M1 and IL-8M10 were observed to be significantly reduced in their ability to activate isolated human neutrophils, suggesting that separate mechanisms may exist by which myeloid progenitor cells and neutrophils are affected by chemokines.

Amino Acid Sequence↗
PubMed1993

Higher-affinity oligosaccharide ligands for E-selectin.

A series of synthetic oligosaccharides based on sialyl Lewis x (sLex; Neu5Ac alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc) and sialyl Lewis a (sLea; Neu5Ac alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNAc) was used to study the binding interactions of selectins. E-selectin-immunoglobulin fusion protein (E-selectin-Ig) bound to immobilized bovine serum albumin (BSA)-neoglycoproteins containing sLex or sLea in a Ca(2+)-dependent manner. Solution-phase sLex tetrasaccharide blocked this interaction by 50% at a concentration of 750 +/- 20 microM (IC50). sLea was more effective (IC50 = 220 +/- 20 microM), while nonsialylated, nonfucosylated derivatives showed little or no activity at concentrations up to 1 mM. Attachment of an 8-methoxycarbonyloctyl aglycone in a beta linkage to the anomeric carbon of the GlcNAc of sLex or sLea increased their blocking activity nearly twofold. Finally, replacement of the 2-N-acetyl substituent of the GlcNAc by an azido or amino group resulted in substantial increases in activity, with the most potent inhibitor being amino substituted sLea, which was 36-fold more active (IC50 = 21 +/- 3 microM) than the reducing tetrasaccharide sLex. In contrast to results obtained with E-selectin-Ig, P-selectin-Ig binding to immobilized BSA-sLea was blocked modestly by most oligosaccharides at 1 mM, with no substantial differences among them. IC50 values of soluble oligosaccharides determined in competitive binding studies accurately predicted blocking of leukocyte adhesion to recombinant E-selectin-Ig and to cytokine-activated endothelium.

Carbohydrate Conformation↗
PubMed1990

Antigen processing of myelin basic protein is required prior to recognition by T cells inducing EAE.

The processing and presentation of whole myelin basic protein (MBP) and a 12 amino acid encephalitogenic peptide were investigated using MBP-immune and peptide-immune murine T cell lines. Myelin basic protein is the major component of central nervous system (CNS) white matter capable of inciting an autoimmune response which leads to the disease, experimental allergic encephalomyelitis (EAE), in a number of animal species. MBP-immune T cell lines caused a form of adoptively transferred EAE when injected into naive, syngeneic recipients. It has been found that both whole MBP and peptide required processing in order to induce proliferation of the T cell lines. The proliferative response was greatest when MBP was processed under conditions in which proteolysis was prevented. The demonstration that activation of encephalitogenic MBP immune T cells requires a processed form of MBP may have relevance to the human inflammatory CNS demyelinating condition, multiple sclerosis, for which EAE is the EAE is the prime animal model.

Amino Acid Sequence↗