Sony Pixel Power calrec Sony

September 21, 2022

22/09/2022

Scripps Research discovery suggests new strategy against harmful inflammation Scientists identify WASH protein complex as a gatekeeper of neutrophil-driven inflammation

September 21, 2022

LA JOLLA, CA A team led by Scripps Research scientists has uncovered key details of an immune-cell process that frequently underlies excessive inflammation in the body. The findings could lead to new ways of preventing and/or treating inflammation-related conditions such as sepsis, arthritis, and coronary artery disease.

In the study, published September 21, 2022 in Nature Communications, the researchers showed that a multi-protein molecular machine called WASH has a powerful role in restraining excessive inflammatory activity by neutrophils, immune cells that are important early responders against infections.

Our findings point to the possibility of future treatments that target this WASH-regulated pathway to inhibit neutrophil-driven inflammation while preserving most of neutrophils' anti-microbial effectiveness, says study senior author Sergio Catz, PhD, professor in the Department of Molecular Medicine at Scripps Research.

Neutrophils are workhorses of the mammalian immune system, comprising about two-thirds of the white blood cells that circulate through our bloodstreams. They combat invading microbes by engulfing and digesting them, and by releasing a variety of antimicrobial molecules via a process called exocytosis.

Many of the antimicrobial molecules that neutrophils release via exocytosis are potent enough to harm healthy cells. There is evidence that excessive and/or chronic release of these molecules at least partly underlies serious medical conditions and types of tissue injury, including the bacterial blood-infection condition known as sepsis, arthritis, reperfusion injury to cells after oxygen deprivation, smoke inhalation injury to lungs, inflammatory bowel disease, some cancers, and even the artery-thickening atherosclerosis that leads to heart attacks and strokes. Yet scientists still have a lot to learn about how this exocytosis process works.

In the new study, Catz and his team illuminated the important role WASH plays in neutrophil exocytosis. Neutrophils, when they encounter signs of infection or inflammation, typically respond initially by releasing, via exocytosis, milder compounds within gelatinase granules capsule-like enclosures named for one of the enzymes found within them. A second type of exocytosis, triggered secondarily and usually only by more severe infection or inflammation, involves the release of azurophilic granules, so-called because they are bound by a common blue stain. Azurophilic cargoes are far more potent and are more likely to damage bystander cells. The team showed that WASH normally facilitates the initial gelatinase granule response, which includes the release of compounds that help neutrophils adhere to and move around surfaces such as blood vessel walls. At the same time, WASH normally restrains the release of toxic azurophilic granules cargoes.

In experiments, neutrophils without WASH released excessive amounts of azurophilic granules. Mice with these neutrophils had blood levels of toxic azurophilic molecules that are normally found in cases of harmful systemic inflammation. The mortality rate of such mice when experiencing an experimental sepsis-like condition was more than triple that of normal mice.

WASH seems to be an important molecular switch that controls neutrophils' responses to infection and inflammation by regulating the release of these two kinds of antimicrobial cargoes, Catz says. When WASH is dysfunctional, the result is likely to be excessive and chronic inflammation.

In this study, using state-of-the-art cell biology approaches, we reveled how neutrophils control their timely response through sequential exocytosis, and have identified a molecular system that acts as the gatekeeper of this process, Catz adds.

Catz and his colleagues are continuing to study WASH and other molecules involved in neutrophil exocytosis, with the goal of finding candidate drug molecules that can damp excessive azurophilic granule exocytosis to treat inflammatory conditions without impairing neutrophils' functions as immune first responders.

The study's co-first authors were Senior Staff Scientist Jennifer Johnson, PhD, and postdoctoral researchers Elsa Meneses-Salas PhD, and Mahalakshmi Ramadass, PhD, all members of the Catz lab during the study.

Differential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation was co-authored by Jennifer Johnson, Elsa Meneses-Salas, Mahalakshmi Ramadass, Jlenia Monfregola, Farhana Rahman, Raquel Carvalho Gontijo, Kersi Pestonjamasp, Dale Allen, Jinzhong Zhang, Kasra Askari, Danni Chen, Juan Yu, Scott Henderson, Nathan Wineinger and Sergio Catz, from Scripps Research; William Kiosses, Yanfang Peipei Zhu and Catherine Hedrick from the La Jolla Institute for Immunology; Douglas Osborne and Daniel Billadeau from the Mayo Clinic; Matilde Valeria Ursini of the Italian National Research Council's Institute of Genetics and Biophysics A. Buzzati Traverso; and Sergio Grinstein of the University of Toronto.

The research was funded in part by the National Institutes of Health (P01HL152958, R01HL088256, R01AR070837, R01DK110162).

Molecular and Cellular Biology Catz, Sergio
LINK: https://www.scripps.edu/news-and-events/press-room/2022/20220921-catz-...
See more stories from scripps

Most recent headlines

05/01/2027

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be demoed at CES 2026

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...

09/10/2026

Dolby Expands Dolby OptiView Platform with New Capabilities at IBC 2026

September 10 2026, 06:00 (PDT) Dolby Expands Dolby OptiView Platform with New Capabilities at IBC 2026 New Sports Intelligence helps providers better unders...

07/10/2026

Dalet Flex LTS Delivers Smarter Media Operations from Ingest to Distribution

Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...

12/09/2026

Calrec expands its IP ecosystem with new Type RT console...

At IBC 2026, Calrec has unveiled Type RT, a new 6, 12 and 18-motorised fader console range that condenses everything a broadcast audio desk needs into a compact...

12/09/2026

Matrox, NVIDIA Integrate ORIGIN, Holoscan For Media

Share Copy link Facebook X Linkedin Bluesky Email...

12/09/2026

Ross Video Debuts New Live Production Technology at IBC2026

Share Copy link Facebook X Linkedin Bluesky Email...

12/09/2026

FCC Nominee Thumann Severs to Testify in Senate Sept. 17

Share Copy link Facebook X Linkedin Bluesky Email...

12/09/2026

TV Skyline Becomes The World's First Ultrix FR30 Customer

Share Copy link Facebook X Linkedin Bluesky Email...

12/09/2026

Ikegami Introduces VN Versions of Four UNICAM XE Cameras At IBC2026

Share Copy link Facebook X Linkedin Bluesky Email...

12/09/2026

Riedel Technology Powers Record Breaking Esports World Cu...

WUPPERTAL, Germany Sept. 11, 2026 From July 6 to Aug. 23, 2026, Paris hosted the Esports World Cup (EWC), a seven-week live production spanning eight stages...

12/09/2026

Mediacom Deploys Riedel Easy5G for Wireless Camera Covera...

Riedel Communications today announced that Mediacom has purchased and deployed Easy5G , Riedel's Private 5G solution, for live broadcast coverage of La Vuel...

12/09/2026

A Decade of Innovation AMP VISUAL TV Builds on Ten Years...

AMP VISUAL TV is continuing the evolution of its production infrastructure with further investments in Riedel technology across its OB fleet and fixed productio...

12/09/2026

Touring Video Expands Flexible Production Workflows With...

Riedel Communications today announced that Touring Video, a premier entertainment mobile production service company, continues to expand its production workflow...

12/09/2026

Atomos Expands Accessory Ecosystem with New SHAPE and Sma...

Atomos (7.B19) today announced new third-party accessories for Sumo PRO-19 and Shinobi 7 II, developed by SHAPE and SmallRig to give production teams more ways ...

12/09/2026

Deity Microphones Brings PR 2ii, TC-2, and D4RX to IBC2026

Deity Microphones Brings PR 2ii, TC-2, and D4RX to IBC2026 Brie Clayton September 11, 2026 0 Comments The Deity PR-2ii arrives with production firmwar...

12/09/2026

Blackmagic Design Announces Special Pricing for Ultra HD Products

Blackmagic Design Announces Special Pricing for Ultra HD Products Brie Clayton September 11, 2026 0 Comments Now customers can afford to upgrade to Ul...

12/09/2026

Grass Valley EDIUS Future Assurance Program launched at IBC2026

Grass Valley EDIUS Future Assurance Program launched at IBC2026 Brie Clayton September 11, 2026 0 Comments New program gives EDIUS customers access to...

12/09/2026

Berklee Students Develop New Ideas for Live Entertainment and Travel in London

Berklee Students Develop New Ideas for Live Entertainment and Travel in London This summer, a group of music business students collaborated with Heathrow, Bri...

11/09/2026

IBC 2026: Calrec Launches Type RT Console and Apex M6 Modular I/O Platform

Calrec will introduce two new products at IBC2026 (Stand 8.C47, RAI Amsterdam, September 11-14): the Type RT broadcast production console and the Apex M6 Modula...

11/09/2026

IBC 2026: Grass Valley Launches AVORA All-in-One Live Production Platform

Grass Valley has announced AVORA, a standalone all-in-one live production solution launching at IBC2026 (Booth 9.A01 and IBC Future Tech Zone, Stand 14.C49, Sep...

11/09/2026

IBC 2026: CAMB.AI Launches Streaming SDK and Dashboard for Multilingual Live Broadcasting

CAMB.AI is introducing its Streaming SDK and Streaming Dashboard at IBC2026, wit...

11/09/2026

IBC 2026: EVS Launches XT-S Software-Defined Multi-Application Server

EVS has announced XT-S, a software-defined server platform that runs multiple live production applications on a common hardware foundation. The platform debuts ...

11/09/2026

IBC 2026: EKT Showcases Linux-Based ATSC 3.0 Converter Box

EKT is demonstrating a new Linux-based ATSC 3.0 set-top box at IBC2026. The second-generation product moves away from Android to reduce memory costs, with Linux...

11/09/2026

IBC 2026: Sennheiser Group to Showcase Wireless, Monitoring, and Broadcast Workflow

The Sennheiser Group will exhibit at IBC2026 (Hall 8, Booth D50, September 11-14...

11/09/2026

Ludacris Joins Chris Stapleton and Cindy Blackman Santana for Monday Night Footballs In the Air Tonight Open

ESPN's Monday Night Football will open its 2026-27 season with a new renditi...

11/09/2026

Dalet Integrates NVIDIA Synthetic Content Detection into Dalet Flex

Dalet has announced an integration of NVIDIA's Synthetic Video Detector AI model into Dalet Flex, enabling media organizations to identify potentially AI-ge...

11/09/2026

IBC 2026: MC-IF Demonstrates VVC Capabilities

The Media Coding Industry Forum (MC-IF) will demonstrate Versatile Video Coding (VVC) capabilities at IBC2026 (Hall 2, Stand 2.B13), as the codec moves toward c...

11/09/2026

IBC 2026: Sony to Demonstrate Live, News, Cinema, and Immersive Production

Sony will exhibit at IBC2026 (Hall 13, September 11-14), demonstrating products across live production, news, cinema, and immersive and spatial content workflow...

11/09/2026

Wave Central Named Recipient of 2026 Technology and Engineering Emmy for FPV Drone Systems

Wave Central, a Domo Broadcast Company, has been named a recipient of a 2026 Tec...

11/09/2026

IBC 2026: SNS Validates EVO Compatibility With Avid Media Composer 2026.8, Adds Browser-Based Upload to Outpost

Studio Network Solutions (SNS) is bringing a pair of workflow updates to IBC2026...

11/09/2026

IBC 2026: iodyne to Demo Pro Mini Smart Drive Across Four Partner Booths

iodyne will co-exhibit with Hedge at IBC2026 (Booth 7.A36, September 11-14) and appear across three additional partner booths, marking the first public demonstr...

11/09/2026

SVG GameDay, Ep. 30: Freelance Graphics Operator Corinne Yamada - Philly-Based Graphics Creation

In-venue and creative video staffers at the professional and collegiate level ha...

11/09/2026

CBS Sports Goes HDR Across Its Entire NFL Package, Heads to Rio in Week 3

The network will phase in HDR crew by crew while expanding Next Gen Stats integration, SkyDry availability, and onsite studio shows...

11/09/2026

IBC 2026: CAMB.AI Unveils the World's First Multilingual Broadcasting Agent Powered by NVIDIA

CAMB.AI is introducing its new Streaming SDK and Streaming Dashboard at IBC2026,...

11/09/2026

Netflix Goes Down Under With NBC Sports, NEP for NFL From Melbourne

Massive host operation at Melbourne Cricket Ground featured 54 cameras, 25,000 ST 2110 flows, REMI studio production in Stamford, and global distribution to mor...

11/09/2026

FOX Sports Homogenizes Coverage With Upscaled Game Tech, Seamless Integration With Studio Shows in L.A.

Production Anywhere Remote Kit (PARK) & AR-fueled Stage B are two key pieces to ...

11/09/2026

Get to Know This Fall and Winter's Filmmakers Through These 36 Sundance Institute-Supported Films

By Ramona Flume and Lucy Spicer There's a particular kind of magic that hap...

11/09/2026

Film Festival Watch: 8 Sundance Institute-Supported Films to See at the 2026 Toronto International Film Festival

By Jessica Herndon The fall film season is kicking off, and Sundance Institute-...

11/09/2026

Positive Grid announce the Spark Pedal

Spark series gains compact modelling stompbox Positive Grid's Spark amps have become a popular part of the company's line-up, offering a convenient ...

11/09/2026

Rapid Flow release omniGRID

New flagship sequencing plug-in revealed Rapid Flow have just launched a new 16-track sequencer plug-in which they say has been designed for total rhythmic...

11/09/2026

Rohde & Schwarz unveils the air-cooled R&STM1 medium-power UHF transmitter at IBC 2026

Rohde & Schwarz unveils the air-cooled R&S TM1 medium-power UHF transmitter at I...

11/09/2026

TV Usage Kicks Usual Summer Slowdown, Fueled by World Cup and Streaming in Nielsen's July Gauge Reports

FIFA World Cup 2026 and Peacock's Love Island USA' Power NBCU-Versant ...

11/09/2026

Atomos Debuts New HDR Monitors at IBC2026

Share Copy link Facebook X Linkedin Bluesky Email...

11/09/2026

Calrec to Unveil Type RT Compact Console at IBC2026

Share Copy link Facebook X Linkedin Bluesky Email...

11/09/2026

Lightware Launches LARA 2 with New Architecture for More...

Lightware has announced the launch of LARA (Lightware Advanced Room Automation) 2.0, a major upgrade to its built-in room automation platform, introducing impro...

11/09/2026

MusiMap launches latest technology unlocking new commerci...

10 September 2026 - MusiMap, the B2B music intelligence company that is transforming how companies can harness the emotional power of music to reach consumers a...

11/09/2026

Matrox Video Integrates Matrox ORIGIN with NVIDIA Holosca...

Matrox Video today announced an integration between Matrox ORIGIN and NVIDIA Holoscan for Media, enabling Matrox ORIGIN media services to be provisioned, config...

11/09/2026

Net Insight brings cloud-native live media orchestration...

Net Insight today announced that its cloud-native live media orchestration is now available through Oracle Cloud Marketplace, providing broadcasters, production...

11/09/2026

Calrec to Unveil Type RT Compact Console at IBC 2026

Share Copy link Facebook X Linkedin Bluesky Email...

11/09/2026

Biggest functionality boost yet makes Buttons the perfect...

Version 1.8 will bring advanced routing control, new workflow tools, boosted control panel flexibility and ease of integration into IP networks...