Cytokines and PGE2 modulate the phagocytic function of the beta-glucan receptor in macrophages

Under serum-free conditions the beta-glucan receptor of mouse macrophages mediates phagocytosis of beta-1,3-D-glucan-coated microbeads (diameter 2 microns). IFN-gamma increases the phagocytic function of the beta-glucan receptor in a dose-dependent manner, giving the plateau level at 100 U/ml. Maximum activity appears 9 h after addition of IFN-gamma to the cells. The effect disappears within 24 h. The effect of IFN-gamma may be a result of augmented receptor synthesis since treatment with cycloheximide reduces the phagocytosis. IL-1 also increases the phagocytic function of the beta-glucan receptor giving a dose-dependent response and with the plateau level reached at 10 U/ml. Maximum activity is found 4 h after addition of IL-1 to macrophages. The effect disappears within 24 h. TNF does not alter the phagocytic function of the beta-glucan receptor, but TNF together with IL-1 prolongs the effect of IL-1. PGE2 reduces the phagocytic function of the beta-glucan receptor. Maximum reduction is achieved with 8 ng/ml. Time-course studies show the lowest phagocytic activity 9 h after addition of PGE2 to the cells.     

NMR structure and mutagenesis of the FADD (Mort1) death-effector domain

When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity.     

Synthesis and biological studies on analogs of cyclolinopeptide A with a shortened peptide chain

Continuing our work on the immunosuppressive activity of cyclolinopeptide A (CLA), a cyclic nonapeptide of the sequence: c-(-Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe), we synthesized a series of 6 linear analogs of CLA, successively shortened at the N-terminus of the peptide chain. Immunosuppressive activity of acetates as well as trifluoroacetates of these peptides was investigated using PFC (humoral immunity) and DTH (cellular immunity) tests. It was found that the immunosuppressive potency of the peptides examined diminishes with shortening of the peptide chain. Octapeptide I with the sequence Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe was found to be the most active of the whole series. The immunosuppressive activity increased again for a tripeptide fragment of CLA of the sequence Pro-Phe-Phe. The immunosuppressive activity of octapeptide probably depends on the suppression of IL-1, IL-6 and TNF production by the cells involved in immune and inflammatory response.     

An automatic machine for bending a furniture fitting tie rod

Translated from Khimicheskoe i Neftyanoe Mashinostroenie, No. 8, pp. 31–32, August, 1992.     

Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family

By using a mRNA differential display technique to search for salicylate suppressible genes, we identified a cDNA in human foreskin fibroblasts, which by GenBankTM DNA data base search shows sequence homology to the recently reported cullin/Cdc53 (CUL) family genes, especially CUL-3. We have cloned the full-length human CUL-3 (Hs-CUL-3) cDNA. It encodes a 768-amino acid polypeptide and has a predicted molecular weight of 88,939. The amino acid sequence of Hs-CUL-3 shows 46% homology to that of its Caenorhabditis elegans ortholog, Ce-CUL-3, and 27 and 23% to that of Hs-CUL-1 and Hs-CUL-2, respectively. Northern blot analysis showed that phorbol 12-myristate 13-acetate increased the expression of Hs-CUL-3 mRNA in a concentration- and time-dependent manner, and this increase was inhibited by sodium salicylate. Hs-CUL-3 widely expressed in human tissues and its expression in cultured COLO205 colon cancer cells was increased when compared with that in normal colon cells. It is likely that Hs-CUL-3 is involved in cell proliferation control.     

The role of human leukocyte antigen in susceptibility and clinical manifestations of sarcoidosis

To investigate the association of human leukocyte antigen (HLA) with susceptibility and clinical manifestations of sarcoidosis. Fifty-five patients with sarcoidosis were studied by using allele group specific polymerase chain reaction technique (PCR). Our data show that: (1) the gene frequency of HLA-DR5 is significantly increased in patients with sarcoidosis, but that of HLA-DR7 decreased. (2) Gene frequencies of HLA-DR9 and HLA-DR5 are relatively increased in male patients and in patients with stage I and stage IIa, respectively. The results suggest that HLA-DR gene might contribute to the susceptibility as well as to the difference of clinical manifestations in sarcoidosis.