Videos

New Medicines for Autoimmune Diseases [HMS]

The discovery of integrins by HMS Professor Timothy Springer and others in the field led to a new class of treatments for autoimmune disorders. Integrins are essential adhesion molecules on the surface of cells. They help cells decide what to become, where to go, how to respond to their environments, and when to grow, divide, or die. Their dysfunction can contribute to a range of diseases. The FDA has approved drugs that reduce the activity of specific integrins to treat autoimmune disorders such as multiple sclerosis, ulcerative colitis, and Crohn’s disease, and for certain blood-clotting conditions. Without federal funding and support for the research, these drugs would not have been developed, says Springer.

All three steps can be reconstituted in vitro. Both P-selectin and ICAM-1 are incorporated on the wall of a flow chamber. Neutrophils are infused and begin rolling on the P-selectin. There is no interaction with ICAM-1, because the aMb2 and aLb2 integrins on the neutrophil have not been activated. Subsequently, a chemoattractant such as a bacterial N-formylated peptide (fMLP) is added to the perfusate. When it reaches the position of the rolling neutrophils in the flow chamber, it rapidly activates G protein-coupled receptor signaling pathways, which activate integrins, resulting in firm adhesion to the ICAM-1. The video segment is a time-lapse that is accelerated 6-fold. Lawrence, M. B., and Springer, T. A. (1991). Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins, Cell 65, 859-873.