![Sample our Health and Social Care journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5938/TOC-Subject-Sample-2021-Health-Social-Care.jpg"})
Abstract
Inflammation is a crucial response against invading pathogens, in which immune cells, including neutrophils and T cells, are recruited into tissue from the bloodstream to help clear infection. However, a prevailing inflammatory response where the immune cells attack healthy tissue is associated with many diseases, including asthma, rheumatoid arthritis, atherosclerosis and multiple sclerosis. Integrins are key players in the recruitment of immune cells from the bloodstream into tissues, and are thus therapeutic targets for intervention with inflammatory responses. Thus far, mainly extracellularly acting therapeutics (monoclonal antibodies) have been developed against integrins, targeting ligand binding sites in these heterodimeric adhesion receptors. However, since these therapeutics nonselectively block all integrin functions, some side effects are expected and have been observed. Therefore, novel concepts need to be developed in the therapeutic targeting of integrins. Recently, major advances have been made in the understanding of integrin biology. Integrin structures have been solved by X‐ray crystallography, revealing unexpected data about the activation mechanism of integrins in cells. Additionally, several intracellular factors in the integrin activation process have been identified, providing potential specific targets for therapeutic intervention. Here, we present key events and players in leukocyte integrin activation, and discuss potential new drug targets in the prevention of inflammatory disease.
| Abbreviations | ||
| Arf‐GAP | = | ADP‐ribosylation factor GTPase‐activating protein |
| ECM | = | extracellular matrix |
| GTP | = | guanosine triphosphate |
| ICAM | = | intercellular adhesion molecule |
| LAD‐1 | = | leukocyte adhesion deficiency‐I |
| MMP | = | matrix metalloprotease |
| Rac | = | Ras‐related C3 botulinum toxin substrate |
| RhoA | = | Ras homolog gene family, member A |
| TCR | = | T cell receptor |
| VCAM‐1 | = | vascular cell adhesion molecule‐1 |
| Abbreviations | ||
| Arf‐GAP | = | ADP‐ribosylation factor GTPase‐activating protein |
| ECM | = | extracellular matrix |
| GTP | = | guanosine triphosphate |
| ICAM | = | intercellular adhesion molecule |
| LAD‐1 | = | leukocyte adhesion deficiency‐I |
| MMP | = | matrix metalloprotease |
| Rac | = | Ras‐related C3 botulinum toxin substrate |
| RhoA | = | Ras homolog gene family, member A |
| TCR | = | T cell receptor |
| VCAM‐1 | = | vascular cell adhesion molecule‐1 |
Acknowledgements
The original work in the authors' laboratory has been supported by The Academy of Finland, the Sigrid Juselius Foundation, the Finnish Cancer Society, the Magnus Ehrnrooth Foundation and Medicinska understödsföreningen Liv och Hälsa.