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Biomedical subjects

S D Wright

Publications and source records attributed to S D Wright.

151 records · Page 9Linked to original sources
PubMed1982

Human neutrophil Fc gamma receptor distribution and structure.

Fc receptors (FcR) for IgG on human cells were analyzed with two monoclonal antibodies, 3G8 and 4F7. Fab fragments of both hybridoma IgGs inhibited binding to neutrophils of soluble rabbit IgG complexes and sheep erythrocytes (E) coated with rabbit IgG. The number of sites for 3G8 Fab was 135,000 per neutrophil, roughly equivalent to the number of sites for rabbit IgG in immune complexes (112,000 per cell). We did not observe human IgG1 binding sites on neutrophils, although binding of IgG1 to FcR-bearing lines U937 and HL-60 was readily demonstrated. Other cell types bearing 3G8 binding sites were mature chronic myelogenous leukemia cells, eosinophils, 6% of E-rosetting lymphocytes, and 15% of Ig-bearing peripheral lymphocytes. No binding of 3G8 Fab was observed on the FcR-bearing cell lines U937, HL-60 Raji, Daudi, and K562 or on blood monocytes. However, 15% of monocytes cultured for 7 days and 60% of lung macrophages expressed 3G8 antigen. When analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the neutrophil FcR immunoprecipitated with 3G8 or 4F7 Fab-Sepharose displayed a broad band extending from Mr 73,000 to 51,000; in many experiments this band was resolved into two poorly separated components, centered at Mr 66,000 and 53,000. These results show that human neutrophil FcR for IgG is different from that on monocytes, with respect to both antigenic composition and binding of monomeric IgG1.

Antibodies, Monoclonal↗
PubMed1981

How complement kills E. coli. I. Location of the lethal lesion.

We have studied the action of human complement (C) on E. coli membranes. We find, as have others, that C disrupts the outer membrane (OM), allowing the release of periplasmic proteins. In addition, we have found 1) that in the complete absence of lysozyme, C damages the inner membrane (IM), 2) IM damage is different from OM damage in that only small molecules traverse a damaged IM whereas macromolecules traverse damaged OM, 3) IM damage and OM damage occur with identical kinetics and dose response, suggesting that IM and OM damage are closely coupled events, and 4) upon the addition of purified C8 and C9 to the washed cellular intermediate, E. coli C 1-7, both IM and OM are damaged coordinately. These results, taken together, suggest that C damages E. coli membranes by acting at a site contiguous with both membranes. We speculate that C may simultaneously gain access to both membranes by acting at the junctions between IM and OM.

Alkaline Phosphatase↗
PubMed1981

How complement kills E. coli. II. The apparent two-hit nature of the lethal event.

We have studied the nature of complement (C) action on red blood cells and E. coli with respect to the number of "hits" required for membrane damage. Our method of analysis involves adding various amounts of purified C7 or C8 to serum preparations immunochemically depleted of C7 or C8, respectively, in order to construct dose-response curves for the action of C's terminal complex. The shape of the dose-response curves reflects the single or multiple-hit nature of C action. Our method confirms that C acts on red cells by a 1-hit mechanism, whether measured by lysis or by the permeation of a small molecule. In contrast, we find with E. coli that C-mediated outer membrane damage, inner membrane damage, and killing all appear to require more than 1 hit. We have also discovered a property of E. coli that displays a nonlethal 1-hit response to C that is particularly useful in the analysis of multiple-hit dose-response curves. Simultaneous measurements of this single-hit phenomenon and the multiple-hit killing of E. coli allow us to make direct comparisons of the amount of C needed for each response. On the basis of the midpoints of the single and multiple-hit curves, C-mediated membrane damage and killing of E. coli appear to be a 2-hit process.

Animals↗
PubMedDate not supplied

Phagocytosing macrophages exclude proteins from the zones of contact with opsonized targets.

During receptor-mediated phagocytosis, macrophages release toxic molecules such as hydrogen peroxide which enable them to kill antibody-coated tumour cells and parasites, too large to consume. Previous workers observed that while peroxide was clearly responsible for cytolysis of certain antibody-coated tumour cells, extracellular catalase was unable to inhibit this cytolysis, and they suggested that macrophages secrete peroxide into a protected cleft between the phagocyte and target. We have tested this and report here that the space beneath macrophages spread on glass surfaces is accessible to proteins with a molecular weight (MW) as large as 200,000 but the space beneath macrophages plated on glass surfaces coated with phagocytosis-promoting ligands is impermeable to proteins as small as 50,000 MW. It appears indeed that macrophages form a protein-tight seal at the periphery of their contact with ligand-coated surfaces and thereby create a closed compartment between the cell and the target.

Cell Adhesion↗
PubMedDate not supplied

Cellular strategies in receptor-mediated phagocytosis.

Two strategies by which mononuclear phagocytes restrict and localize their microbicidal capacities are reviewed. The first concerns the ability of macrophages to seal off a closed compartment between themselves and opsonized targets. This compartment may be used to contain, concentrate, and protect toxic substances secreted by the phagocyte. The second concerns the ability of macrophages to regulate the phagocytosis-promoting capacity of their C3 receptors. C3 receptors are maintained in an inactive state, but they can be readily activated at sites of infection in such a way that they promote vigorous phagocytosis.

Complement C3↗
PubMedDate not supplied

Brevetoxicosis in manatees (Trichechus manatus latirostris) from the 1996 epizootic: gross, histologic, and immunohistochemical features.

In 1996, at least 149 manatees (Trichechus manatus latirostris) died in an unprecedented epizootic along the southwest coast of Florida. At about the same time, a bloom of the brevetoxin-producing dinoflagellates, Gymnodinium breve, was present in the same area. Grossly, severe nasopharyngeal, pulmonary, hepatic, renal, and cerebral congestion was present in all cases. Nasopharyngeal and pulmonary edema and hemorrhage were also seen. Consistent microscopic lesions consisted of catarrhal rhinitis, pulmonary hemorrhage and edema, multiorgan hemosiderosis, and nonsuppurative leptomeningitis. Immunohistochemical staining using a polyclonal primary antibody to brevetoxin (GAB) showed intense positive staining of lymphocytes and macrophages in the lung, liver, and secondary lymphoid tissues. Additionally, lymphocytes and macrophages associated with the inflammatory lesions of the nasal mucosa and meninges were also positive for brevetoxin. These findings implicate brevetoxicosis as a component of and the likely primary etiology for the epizootic. The data suggest that mortality resulting from brevetoxicosis may not necessarily be acute but may occur after chronic inhalation and/or ingestion. Immunohistochemical staining with interleukin-1-beta-converting enzyme showed positive staining with a cellular tropism similar to GAB. This suggests that brevetoxicosis may initiate apoptosis and/or the release of inflammatory mediators that culminate in fatal toxic shock.

Adrenal Glands↗