1
and dietary supplements. Thus, it will keep the research activities that support- ed its nutrition division and are linked to its agricultural biotechnology and phar- maceuticals businesses. In 2000, for example, Monsanto an- ticipates launching plant-based sterols for cardiovascular health. It also antici- pates launching one or more nutritional or modified crop products each year. Ann Thayer Molecular movies capture first steps of immune response Researchers at Washington Universi- ty School of Medicine, St Louis, and Stan- ford University School of Medicine have made an unusual video that captures the molecular rearrangements that are among thefirststeps in the immune system's re- sponse to a foreign substance. By attaching fluorescent labels to dif- ferent peptides found on the surface of an antigen-presenting cell, graduate student Arash Grakoui, associate professor of pa- thology Michael L Dustin, and their col- leagues can watch these peptides move around to form a precise bull's eye pattern that enables these cells to bind to helper T lymphocytes (T cells), activating the im- mune system [Science, 285, 221 (1999)]. When bacteria or other foreign sub- stances enter the body, they are quickly scavenged by dendritic cells or macro- phages that circulate in the blood. These cells degrade the invader into peptide fragments (antigens), which, together with membrane proteins, form an anti- gen-presenting complex on the surface of the cell. T cells rapidly and exquisitely recognize which of these complexes con- tain foreign antigens, bind to them, and initiate an elaborate series of biochemical responses that activate the immune sys- tem tofightoff the invader. The new mov- ies provide the first dynamic view of the criticalfirstfew minutes of the interaction between the two cells. "We can watch the decision-making process that the T cell goes through to determine whether or not it's going to mount a response to an antigen," says Dustin, who, like Grakoui, is at Wash- ington University. Although the researchers use actual T cells in their experiment, they use a mod- el for the plasma membrane of the anti- gen-presenting cell. Fluorescently la- Like a miniature spacecraft, a T ceii (blue) docks on the surface of a dendritic cell in this conceptualization of the first steps of an immune response. The red and green bull's eye represents the molecular landing site shared by the two cells. The molecules (adhesion proteins shown in red and antigen-presenting complexes in green) are actually on the dendritic cell, but the presence of the hovering T cell causes them to arrange in this pattern. beled antigen complexes and a second type of cell-surface molecule—an adhe- sion protein—are incorporated into a lip- id bilayer on a glass support. These mole- cules can move about freely on the glass plate, as they would in an actual cell mem- brane. (The web movie of this motion can be seen at http://www.sciencemag.org/ feature/data/1040037.shl.) Earlier work by others had shown that within the first half hour of contact, ad- hesion molecules and anti- gen-presenting ones form a bull's eye pattern, with the antigen-presenting mole- cules in the center of a ring of adhesion molecules. That same pattern is seen in the video images. However, the video shows that several steps are involved in forming this initial pattern. Within 30 seconds, the T cells begin to attach to the membrane sur- face and induce the labeled proteins in the membrane to form patterns. The first pat- tern to form is an inversion of thefinalbull's eye, with the adhesion proteins in the cen- ter and the antigen-present- ing complexes surrounding them. Over the next five minutes, the two change places. "What surprised us is how really dynamic this process is," Dustin says. "It seems like the structure the T cell is building is the critical event," Dustin adds. "Once it has generated this bull's eye pattern, the T cell is fully activated." Rebecca Rawls EPA targets 33 toxic urban air pollutants Last week, the Environmental Protec- tion Agency announced a strategy to further reduce toxic air emissions. The agency says the plan, part of the nation- al air toxics program, will increase pub- lic health protection. This is the next step needed "to pro- tect the millions of people who live in ar- eas where concentrations of toxic air pol- lutants are too high," EPA Administrator Carol M. Browner said in a statement. The Integrated Urban Air Toxics Strategy identifies 33 toxic air pollut- ants—all known or suspected to cause cancer or other health problems—that pose the greatest threat to public health in large urban areas. Included on the list are benzene, mercury, and polychlori- nated biphenyls. The strategy also identifies 29 source categories that are responsible for most of these urban area emissions. EPA has regulations in place or under develop- ment for 16 of these area sources and is targeting the other 13 categories for re- ductions over the nextfiveyears, includ- ing industrial inorganic and organic chemical manufacturing, plastic materi- als and resins manufacturing, and mer- cury cell chlor-alkali plants. The strategy, which is based on mul- tiple sections of the Clean Air Act, has four components: • Regulations that address sources of air toxics at the national and local level. National and local initiatives to ad- dress specific pollutants and to identify specific community risks. • Expanded air toxics monitoring to identify and prioritize areas of concern and to track progress. • Education and outreach programs. The strategy aims to reduce cancer risks by 75% from 1990 levels and to sub- stantially reduce noncancer risks such as birth defects and reproductive ef- fects, particularly among low-income and minority communities dispropor- tionately affected by air toxics. The plan, which will appear in the Fed- eral Register, is available on the Internet at http://www.epa.gov/ttn/uatw/urban/ urbanpg.html. Julie Grisham JULY 12,1999 C&EN 7

Molecular movies capture first steps of immune response

  • Upload
    rebecca

  • View
    212

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Molecular movies capture first steps of immune response

and dietary supplements. Thus, it will keep the research activities that support­ed its nutrition division and are linked to its agricultural biotechnology and phar­maceuticals businesses.

In 2000, for example, Monsanto an­ticipates launching plant-based sterols for cardiovascular health. It also antici­pates launching one or more nutritional or modified crop products each year.

Ann Thayer

Molecular movies capture first steps of immune response

Researchers at Washington Universi­ty School of Medicine, St Louis, and Stan­ford University School of Medicine have made an unusual video that captures the molecular rearrangements that are among the first steps in the immune system's re­sponse to a foreign substance.

By attaching fluorescent labels to dif­ferent peptides found on the surface of an antigen-presenting cell, graduate student Arash Grakoui, associate professor of pa­thology Michael L Dustin, and their col­leagues can watch these peptides move around to form a precise bull's eye pattern that enables these cells to bind to helper T lymphocytes (T cells), activating the im­mune system [Science, 285, 221 (1999)].

When bacteria or other foreign sub­stances enter the body, they are quickly scavenged by dendritic cells or macro­phages that circulate in the blood. These cells degrade the invader into peptide fragments (antigens), which, together with membrane proteins, form an anti­gen-presenting complex on the surface of the cell. T cells rapidly and exquisitely recognize which of these complexes con­tain foreign antigens, bind to them, and initiate an elaborate series of biochemical responses that activate the immune sys­tem to fight off the invader. The new mov­ies provide the first dynamic view of the critical first few minutes of the interaction between the two cells.

"We can watch the decision-making process that the T cell goes through to determine whether or not it's going to mount a response to an antigen," says Dustin, who, like Grakoui, is at Wash­ington University.

Although the researchers use actual T cells in their experiment, they use a mod­el for the plasma membrane of the anti­gen-presenting cell. Fluorescently la-

Like a miniature spacecraft, a T ceii (blue) docks on the surface of a dendritic cell in this conceptualization of the first steps of an immune response. The red and green bull's eye represents the molecular landing site shared by the two cells. The molecules (adhesion proteins shown in red and antigen-presenting complexes in green) are actually on the dendritic cell, but the presence of the hovering T cell causes them to arrange in this pattern.

beled antigen complexes and a second type of cell-surface molecule—an adhe­sion protein—are incorporated into a lip­id bilayer on a glass support. These mole­cules can move about freely on the glass plate, as they would in an actual cell mem­brane. (The web movie of this motion can be seen at http://www.sciencemag.org/ feature/data/1040037.shl.)

Earlier work by others had shown that within the first half hour of contact, ad­hesion molecules and anti­gen-presenting ones form a bull's eye pattern, with the antigen-presenting mole­cules in the center of a ring of adhesion molecules. That same pattern is seen in the video images. However, the video shows that several steps are involved in forming this initial pattern. Within 30 seconds, the T cells begin to attach to the membrane sur­face and induce the labeled proteins in the membrane to form patterns. The first pat­tern to form is an inversion of the final bull's eye, with the adhesion proteins in the cen­ter and the antigen-present­

ing complexes surrounding them. Over the next five minutes, the two change places. "What surprised us is how really dynamic this process is," Dustin says.

"It seems like the structure the T cell is building is the critical event," Dustin adds. "Once it has generated this bull's eye pattern, the T cell is fully activated."

Rebecca Rawls

EPA targets 33 toxic urban air pollutants Last week, the Environmental Protec­tion Agency announced a strategy to further reduce toxic air emissions. The agency says the plan, part of the nation­al air toxics program, will increase pub­lic health protection.

This is the next step needed "to pro­tect the millions of people who live in ar­eas where concentrations of toxic air pol­lutants are too high," EPA Administrator Carol M. Browner said in a statement.

The Integrated Urban Air Toxics Strategy identifies 33 toxic air pollut­ants—all known or suspected to cause cancer or other health problems—that pose the greatest threat to public health in large urban areas. Included on the list are benzene, mercury, and polychlori-nated biphenyls.

The strategy also identifies 29 source categories that are responsible for most of these urban area emissions. EPA has regulations in place or under develop­ment for 16 of these area sources and is targeting the other 13 categories for re­ductions over the next five years, includ­ing industrial inorganic and organic

chemical manufacturing, plastic materi­als and resins manufacturing, and mer­cury cell chlor-alkali plants.

The strategy, which is based on mul­tiple sections of the Clean Air Act, has four components:

• Regulations that address sources of air toxics at the national and local level.

• National and local initiatives to ad­dress specific pollutants and to identify specific community risks.

• Expanded air toxics monitoring to identify and prioritize areas of concern and to track progress.

• Education and outreach programs. The strategy aims to reduce cancer

risks by 75% from 1990 levels and to sub­stantially reduce noncancer risks such as birth defects and reproductive ef­fects, particularly among low-income and minority communities dispropor­tionately affected by air toxics.

The plan, which will appear in the Fed­eral Register, is available on the Internet at http://www.epa.gov/ttn/uatw/urban/ urbanpg.html.

Julie Grisham

JULY 12,1999 C&EN 7