No abstract

There is increasing evidence that leukocyte-endothelial adhesion molecules are important in inflammatory airway disease because of their involvement in the primary steps of entrapment and migration of leukocytes to the site of inflammation. Recently, circulating forms of these adhesion molecules have been described, although their origin, fate, and function are still unknown. We have used an antigen capture ELISA to measure the concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin), and vascular cell adhesion molecule-1 (cVCAM-1) in the peripheral blood of 13 atopic and 16 non-atopic normal subjects, 29 patients with stable asthma, and inpatients with acute asthma on Day 1 (n = 38), Day 3 (n = 29), and Day 28 (n = 13) of an asthmatic episode. Circulating ICAM-1 and E-selectin levels were significantly raised in acute asthma on all three study days when compared with those observed in stable asthma, atopic normal, or nonatopic normal volunteers with no significant differences among the latter three groups. Circulating VCAM-1 was not significantly increased in any of the groups studied. There were no correlations among the concentrations of these three circulating adhesion molecules. The elevated concentrations of cICAM-1 and cE-selectin in acute asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbations of the disease with airway obstruction. It is possible that the cytokine and mediator profiles in acute asthma lead to the preferential synthesis and expression of these two circulating adhesion molecules in comparison with cVCAM-1.

Human immunodeficiency virus (HIV) gene expression is regulated by both general transcription factors and factors induced by activation of T lymphocytes such as NF-KB and the nuclear factor of activated T cells (NFAT). Within the HIV long terminal repeat (LTR), two purine-rich domains between nucleotides -283 and -195 have homology to a regulatory region found in the interleukin 2 promoter, which binds NFAT and other cellular factors. In the HIV LTR, this region has been demonstrated to have both positive and negative regulatory effects on HIV gene expression. In an attempt to clone genes encoding cellular factors that bind to these NFAT-like elements in the HIV LTR, we used Agtll expression cloning with oligonucleotides corresponding to these binding motifs. A ubiquitously expressed cDNA encoding a 60-kDa protein, which we termed interleukin binding factor (ILF), binds specifically to these purine-rich motifs in the HIV LTR. This factor also binds to similar purine-rich motifs in the interleukin 2 promoter, though with lower affinity than to HIV LTR sequences. Sequence analysis reveals that the DNA binding domain of ILF has strong homology to the recently described fork head DNA binding domain found in the Drosophila homeotic protein fork head and a family of hepatocyte nuclear factors, HNF-3. Other domains found in ILF include a nucleotide binding site, an N-glycosylation motif, a signal for ubiquitin-mediated degradation, and a potential nuclear localization signal. These results describe a DNA binding protein that may be involved in both positive and negative regulation of important viral and cellular promoter elements.

Vaccinia virus (W) was successfully used as a live vaccine to eradicate smallpox, but the nature of viral proteins involved in eliciting viral immunity has not yet been identified. A potential candidate is a 14-kDa W envelope protein that is involved in virus penetration at the level of virus-cell fusion, in cell-cell fusion late in infection, and in virus dissemination. The 14-kDa envelope protein has been produced in Escherichia coli, with properties similar to those of the native protein found in the virus particle and in infected cells (C.

The nature of interaction between vaccinia virus and the surface of host cells as the first step in virus infection is undefined. A 32-kDa virus envelope protein has been identified as a cell surface binding protein (