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
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
07/10/2026
Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
16/07/2026
33 leading exhibitors are taking part in the GREAT Britain and Northern Ireland Pavilions and linked locations across IBC2026 (Amsterdam RAI, 11 14 September)...
16/07/2026
Hitomi Broadcast will introduce Spectra, a new HDR colour verification solution measured in picture, not using VPID, at IBC2026 (Hall 10, Stand A40). Expanding ...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
16/07/2026
Zixi, a leader in live video delivery and workflow orchestration, and Comcast Technology Solutions (CTS) today announced a strategic new integration to deliver ...
16/07/2026
Blackmagic Design Cameras Capture Immersive Flight for New Cirrus App
Brie Clayton July 15, 2026
0 Comments
Leader in Personal Aviation taps URSA Cin...
16/07/2026
XenData Announces LTO Archive Appliances with both File and S3 Object Storage In...
16/07/2026
Together the semi-finals had a combined reach of 1.98 million unique individuals...
15/07/2026
The 2026 FIFA World Cup is a big deal for DAZN, which has distribution rights in three markets: Italy, Spain, and Japan. Each requires a different editorial app...
15/07/2026
As sports-media organizations manage rapidly growing content libraries and incre...
15/07/2026
HBS director of digital Johannes Franken talks SVG Europe through the operation built to serve FIFA World Cup 2026 rights holders remotely from Stratford, east ...
15/07/2026
IBC has unveiled the conference program for IBC2026, with this year's event ...
15/07/2026
Software-defined wideband RF platform supports 96-kHz monitoring, streamlined fr...
15/07/2026
New AI-powered module enables broadcasters and content owners to extract dialogu...
15/07/2026
Weeklong gathering at EBU headquarters will test new IPMX capabilities and expand certified product ecosystem...
15/07/2026
Force Tech has announced the appointment of Bryan Adams, CTS, as Vice President of Integration. Adams will oversee AV and broadcast integration project delivery...
15/07/2026
USA Sports has announced an exclusive English-language agreement with the Bundes...
15/07/2026
ITV Sport's FIFA World Cup 2026 coverage has been produced from one of the m...
15/07/2026
Program will provide professional camera kits, training, and technical support to participating local newsrooms...
15/07/2026
San Francisco church becomes first U.S. deployment of the 2 M/E production switcher...
15/07/2026
Former ESPN and NFL Network executive to advise startup league on media, distribution, technology, and fan engagement...
15/07/2026
The Houston-based RSN is the live-game home of the Astros and Rockets...
15/07/2026
Launched alongside new FreqSoft installer
Designed to bridge the gap between hardware and software, Freqport's FreqInOut FO1 unit provides a simple way ...
15/07/2026
Save up to 55% on software until 23 July 2026
Expressive E have just launched their Summer Offer sale, with discounts of up to 55% now applied across their ...
15/07/2026
Real-time stem-separation tool updated
zplane have recently released a new and improved version of their real-time stem-separation plug-in which they say ma...
15/07/2026
A new benchmark in bass enhancement
Described as a new benchmark in bass enhancement , Baby Audio's latest release has been designed to augment the lo...
15/07/2026
DMC Production's AR 1 and AR 2 units reverse the conventional OB workflow, keeping all production-critical processing at the venue while operators work remo...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
GigaCloud, a leading Ukrainian cloud service provider, and Cubbit, the first geo-distributed cloud storage enabler, today announced a new Business Alliance Part...
15/07/2026
SMPTE, the global society for media professionals, technologists, and engineers, has announced the launch of the SMPTE 110th Anniversary Campaign, a fundraising...
15/07/2026
Studio Technologies, a leading manufacturer of high-quality audio, video, and fiber-optic solutions, unveils the new StudioComm Model 762 Stereo Level Control, ...
15/07/2026
COW Jobs: Producer, Virtual Events - Hybrid, Full Time, Salaried
Brie Clayton July 15, 2026
0 Comments
Producer, Virtual Events (Hybrid | Full-time | ...
15/07/2026
Brazilian media organization builds nationwide CDN with Broadpeak's high-performance software for low-latency streaming and new content distribution service...
15/07/2026
DHD announces a new utility designed to increase the efficiency of its audio mixing systems during initial installation and subsequent configuration.
Anyone w...
15/07/2026
BCNEXXT Brings Next-Generation Vipe to IBC2026, Breaking the 1:1 Channel-to-Server Ratio New innovations liberate broadcasters from legacy playout infrastructur...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
General-purpose robots and autonomous machines are moving from research labs to ...
15/07/2026
Wednesday 15 July 2026
Screeners and press pack now available: Gomorrah: The Or...
15/07/2026
Trinity's Treasures features Ruth Negga, Eleanor McEvoy, and David Norris, a...
15/07/2026
Join geographer Dr Susan Hegarty, Engineer Tim Joyce and Architect Orla Murphy a...
Scripps Research discovery suggests new strategy against harmful inflammation Scientists identify WASH protein complex as a gatekeeper of neutrophil-driven inflammation
