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 ...
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...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
02/07/2026
Blackmagic PYXIS 6K Used to Shoot Director Takahisa Zeze's Cry Out
Brie Clayton July 2, 2026
0 Comments
Highly mobile camera supports tense and de...
02/07/2026
Broadcast Solutions acquires BFE, expanding its lead in European broadcast, medi...
02/07/2026
Berklee Alum and Faculty Perform at Boston Public Library's 250th Anniversar...
02/07/2026
Broadcast Solutions GmbH, a leading systems integrator and provider of innovative solutions for the broadcast media industry, is acquiring BFE Studio und Medien...
02/07/2026
Cinegy GmbH, the premier provider of software-defined television technology, has extended the ingest facility at leading Brazilian sports company LiveMode, work...
02/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
02/07/2026
Standalone processors acknowledged for the innovation and value they bring to Pro AV
Cobalt Digital, a leading designer and manufacturer of signal processing ...
02/07/2026
Synamedia announced today the appointment of Dr Tzvi Gerstl as Chief Executive Officer. Paul Segre, who has served as CEO for the past six years, will transitio...
02/07/2026
Screen Australia backs audience-led filmmaking with new insight-driven initiativ...
02/07/2026
Screen Australia refines guidelines for Narrative Content Development and Docume...
02/07/2026
Maxon Autograph: Introduction to working with Tables
Simon Ubsdell July 1, 2026
0 Comments
An overview of Autograph's ridiculously powerful tables...
02/07/2026
Boston Conservatory's Soir e Breaks Records to Fund Student Scholarships The event achieved 127 percent of its fundraising goal in an evening celebrating ...
02/07/2026
How Adam Rosenwach Pivoted from Music to Med Tech Without Missing a Beat What do the rehearsal room and the boardroom have in common? More than you might thin...
02/07/2026
Summer is heating up - and GeForce NOW is taking players along for the ride.
Start the month with Monopoly: Star Wars Heroes vs. Villains, bringing a galaxy fa...
01/07/2026
Broadcast Management Group (BMG) has announced the appointment of Kathy Samuels ...
01/07/2026
Shade has announced Custom Objects and Automations, a platform expansion releasing June 29, 2026, that adds database and workflow automation capabilities direct...
01/07/2026
FOR-A America has announced the addition of Jaz Wray and Fernando Cruz to its U.S. sales team. Both report to Ernie Leon, Senior VP and Head of Sales and Strate...
01/07/2026
NBC Sports will air all 15 MLB games nationally on Sunday, July 5, across NBC, P...
01/07/2026
Clear-Com has announced a wireless communications upgrade for Jeopardy! and Wheel of Fortune, deploying FreeSpeak II and FreeSpeak Icon systems across both prod...
01/07/2026
England's performance team will use Sony's STATSports APEX GPS tracking system to monitor player physical data in real time during FIFA World Cup 2026 m...
01/07/2026
Adder Technology has announced the appointment of Neil Hillier as Chief Executive Officer, effective July 1, 2026. Hillier succeeds Adrian Dickens, who transiti...
01/07/2026
Bitcentral, Inc. has announced a strategic transaction creating two separate companies. The Production and Playout business will continue as Bitcentral, now own...
01/07/2026
DAZN has announced results from DAZN48, its creator initiative for the FIFA World Cup 2026. Launched in April 2026, the program received thousands of applicatio...
01/07/2026
Sarah Rose, VP, global services, Daktronics (NASDAQ: DAKT), will be inducted into the Information Display and Entertainment Association (IDEA) Hall of Fame at t...
01/07/2026
Gravity Media and the World Economic Forum's production team provided broadc...
01/07/2026
Insight Productions has announced the launch of Insight Storm, a 53-foot mobile broadcast unit built for esports production. The truck is built around a Ross Vi...
01/07/2026
ESPN has announced several content initiatives marking America's 250th anniversary, as part of The Walt Disney Company's Disney Celebrates America pro...
01/07/2026
Eleven production kits, REMI workflows, and cloud distribution bring 40 World Cu...
01/07/2026
The conference also discussed the opportunities offered an industry that is endu...
01/07/2026
The Mountain West Conference has announced the launch of MW , a direct-to-consumer streaming platform powered by Kiswe. The platform will carry live Mountain We...
01/07/2026
New AI Assistant, Multi-channel Audio, ARA2 improvements & more
Tracktion's DAW software has just received its latest major update, gaining a selection ...
01/07/2026
Stammering, stuttering, strangulated tones
The Crow Hill Company's latest creation promises to be the most original sound set they've produced to d...
01/07/2026
Exclusive run of limited-edition modelling pedals
Sweetwater and Andertons M...
01/07/2026
The National Film and Video Foundation (NFVF) is pleased to announce that the ca...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
Manfrotto Introduces UNCOVER, the new premium camera bag collection for modern h...
01/07/2026
Blackmagic Design Powers Houston Tamil Sangam Literacy Competition
Brie Clayton July 1, 2026
0 Comments
Volunteers use ATEM Mini Pro, Blackmagic Desig...
01/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
01/07/2026
PlayBox Technology has published State of Broadcast Infrastructure 2026, an in-depth industry research report examining the technologies, operational challenges...
01/07/2026
LONDON, UK, 1 JULY Jigsaw24 has appointed Alan Henry as Head of Sales for Media and Entertainment, reinforcing its continued investment in helping broadcaster...
01/07/2026
Content Vault, the patent-pending secure content distribution platform protecting high-value media from disclosures, theft and unauthorised access, today announ...
Scripps Research discovery suggests new strategy against harmful inflammation Scientists identify WASH protein complex as a gatekeeper of neutrophil-driven inflammation
