The cellular receptors for poliovirus (PVR) are glycoproteins belonging to the immunoglobulin superfamily. Functional receptors for poliovirus are only expressed by primates; known rodent homologues lack the ability to bind virus due to amino acid differences. Human poliovirus infections are targeted to the gastrointestinal tract and, rarely, to motor neurons in the central nervous system. Available evidence suggests that poliovirus uses only one cellular receptor, implying that the tissue tropism of poliovirus is likely to be related to the expression of the human PVR (hPVR). However, low levels of expression of hPVR-specific mRNAs can be detected in many human tissues other than the apparent target cells. The nonpathogenic function of hPVR is unknown. For a study of the transcriptional control of hPVR expression, we have isolated and characterized the promoter of the hPVR gene. Deletion analysis defined an approximately 280 base pair minimal promoter fragment that: 1) lacks TATA-and CAAT-like elements, 2) is distinguished by a high GC content, and 3) promotes transcription at multiple start sites. The pattern of activity caused by transfection of serial 5 -and 3 -promoter deletions is almost identical in HEp2, HeLa, COS-1, and mouse L929 cells, indicating a similar transcriptional regulation of the hPVR promoter in these cell lines. However, on transfection of Raji cells, a Burkitt's lymphoma cell line harboring a transcriptionally inactive hPVR gene, all promoter reporter constructs tested exerted only residual activity. These results suggest that the cis-element(s) governing cell type-specific hPVR expression resides in the minimal promoter region. We also report the sequences of the promoters of two monkey homologues to hPVR (AGM␣1 and AGM␣2).

Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stem cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8 ؎ 15.4; at day 5, 118.3 ؎ 44.7 ng/mL; P F 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated. J. Leukoc. Biol. 65: 94-101; 1999.

The low levels of complement receptor 1 (CR1) on erythrocytes in autoimmune diseases and AIDS may be due to accelerated loss in the circulation, or to a diminished expression of CR1 on the red cell lineage. Therefore, we analyzed the expression of CR1 on reticulocytes (R) vs erythrocytes (E). Healthy subjects had a significant higher CR1 number per cell on R (919 ± 99 CR1/cell) than on E (279 ± 30 CR1/cell, n = 23), which corresponded to a 3.5- ± 1.3-fold loss of CR1. This intravascular loss was confirmed by FACS analysis, which showed that all R expressed CR1, whereas a large fraction of E was negative. The systemic lupus erythematosus (SLE), HIV-infected, and cold hemolytic Ab disease (CHAD) patients had a CR1 number on R identical to the healthy subjects, contrasting with a lower CR1 on their E. The data indicated a significantly higher loss of CR1 in the three diseases, i.e., 7.0- ± 3.8-, 6.1- ± 2.9-, and 9.6- ± 5.6-fold, respectively. The intravascular loss was best exemplified in a patient with factor I deficiency whose CR1 dropped from 520 CR1/R to 28 CR1/E, i.e., 18.6-fold loss. In one SLE patient and in the factor I-deficient patient, the FACS data were consistent with a loss of CR1 already on some R. In conclusion, CR1 is lost progressively from normal E during in vivo aging so that old E are almost devoid of CR1. The low CR1 of RBC in autoimmune diseases and HIV-infection is due to a loss occurring in the circulation by an active process that remains to be defined.

Gesellschaftliche, wirtschaftliche und technologische Umbrüche stellen das klassische Governance-Verständnis heute auf den Prüfstand. Wie der Spagat gelingt, im Unternehmen für ein stabilisierendes Mindestmaß an Orientierung zu sorgen, aber auch unter hoher Marktdynamik flexibel zu bleiben, beleuchtet Sybille Schwarz aus verschiedenen Blickwinkeln. Diese verknüpft sie zu einer multiperspektivischen Governance-Betrachtung. Eine Einladung zum Perspektivwechsel für Aufsichtsräte und Entscheidungsträger, um Chancen und Risiken eingesetzter Governance-Strukturen organisationsgerecht zu beurteilen.

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