Marina Kardell

The role of intracellular calcium regulators in integrin activation and leukocyte recruitment

An infection is always accompanied by rapid leukocyte recruitment from the bloodstream into the inflamed tissue. It defines a coordinated cascade of steps necessary for a sufficient immune response. Within the leukocyte recruitment cascade, one essential step is integrin activation. GTPases as well as GTPase activators and inhibitors play important roles for the regulation of the cascade. GTPases and their mediators are involved in the activity regulation of various of adhesion molecules on the leukocyte surface. However, the exact signaling pathways and their distinct role within the activity regulation is undiscovered.

It has been demonstrated that GTPases are involved in the inositol-1,4,5 triphosphate (IP3) generation and its following induced calcium release due to the receptor engagement in neutrophils. Store operated calcium entry (SOCE) is a major mechanism in calcium influx regulation and is dependent on the calcium-sensing proteins of the STIM family and ORAI- calcium channels.

Previous studies indicate that STIM1 and ORAI1 are required for chemokine-induced LFA-1 activation and neutrophil arrest in vitro and in vivo, suggesting an important function in the intracellular calcium homeostasis during integrin activation and leukocyte recruitment. Therefore, we aim to further investigate the molecular mechanism involved in the intracellular calcium homeostasis and the consequences for leukocyte recruitment.