Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Restless cells: Cause of serious genetic disease discovered - Mouse mutant essential for identification of the responsible gene

White blood cells (leukocytes) are constantly streaming through our vasculature, searching for pathogens - however, in order to trigger an immune response they need to leave the vessels and migrate into the infected tissue.

In patients suffering from the hereditary disease LAD III (leukocyte adhesion deficiency) this passage is blocked. The cause of this defect has now been elucidated by collaborations between the Max-Planck-Institute of Biochemistry, the Cancer Research UK London Research Institute and the LMU Munich: The protein kindlin-3 is essential to arrest leukocytes on vessel walls of inflamed tissues - if it is lacking, transmigration of leukocytes into tissue is impossible.

White blood cells (leukocytes) are cells of the immune system defending the body against infections. By using the vasculature as transportation routes, they can - on the one hand - easily scan the entire body for pathogens in short time. On the other hand, they have to overcome a fundamental problem: Infections are localized mostly in tissues, not within vessels.

Therefore leukocytes have to leave vessels at specific sites and migrate into the tissue in order to fight pathogens. While searching for pathogens, they roll along the vascular wall and establish initially only loose contact with vascular wall endothelial cells. If leukocytes get alarmed by signal molecules presented by the endothelial cells, they bind themselves firmly to the endothelial cell and transmigrate into the tissue.

The so-called integrins - a familiy of proteins expressed on the surface of almost all cells - play a central role in this process. Reinhard Fässler, the head of the department "Molecular Medicine" of the Max-Planck-Institute of Biochemistry in Martinsried and his team study these proteins. In order to migrate into the tissue, leukocytes have to "cast anchor" on the vascular endothelial cells by activating integrins as "anchor molecules". If the adhesion does not work correctly, the leukocytes will be swept away incessantly by the blood flow. "Integrin activation is vital for the adhesion of leukocytes to endothelial cells and also for the aggregation of platelets" explains Max Planck scientist Markus Moser.

Severe infections and an increased risk of bleeding are typical symptoms of the rare recessive hereditary disease LAD III (leukocyte adhesion deficiency syndrome). LAD III is caused by a gene mutation that results in defective leukocytes adhesion: Although integrins are present on the cell surface, they cannot be activated and binding to the vascular endothelial cells is impossible.

The gene defect responsible for the malfunction has so far been unclear. In order to shed light on this question, the Max Planck scientists are investigating proteins that regulate the activation of integrin. A hot candidate was the protein kindlin-3 as it directly binds to integrins. A collaboration between the scientists from the Max-Planck-Institute of Biochemistry and scientists from Cancer Research UK London Research Institute and the Ludwig-Maximilians-University Munich has now been able to prove the essential role of kindlin-3: In mice engineered to lack the kindlin-3 gene leukocytes were no longer able to adhere to the vascular walls and in addition, the mice showed a severe bleeding disorder. "Our results with the kindlin-3 mice gave the crucial hint that mutations in the kindlin-3 might be responsible for LAD III", Moser points out. This finding was then confirmed by clinical studies: In collaboration with Moser and PhD student Siegfried Ussar a team of scientists at the Cancer Research UK London Research Institute discovered that the patients' cells produced no kindlin-3 and, importantly, that their adhesion malfunction could be repaired by expressing normal kindlin-3.

Weitere Informationen:
- Research Group Dr. Markus Moser
- Department of Molecular Medicine, Prof. Dr. Reinhard Faessler
- Press release
- Original publication Moser
- Original publication Svensson

Eva-Maria Diehl | Max-Planck-Gesellschaft
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>