title: Regulation of tissue infiltration by neutrophils: role of integrin α3β1 and other factors.
abstract: OBJECTIVE
  Neutrophils have traditionally been viewed in the context of acute infection and inflammation forming the first line of defense against invading pathogens. Neutrophil trafficking to the site of inflammation requires adhesion and transmigration through blood vessels, which is orchestrated by adhesion molecules, such as β2 and β1-integrins, chemokines, and cytokines. The review focuses on recent advances in understanding the regulators of neutrophil recruitment during inflammation in both acute and chronic settings.
  
  
  RESULTS
  Recent findings suggest that besides the established pathways of selectin or chemokine-mediated integrin activation, signaling by distinct Toll-like receptors (TLRs) (especially TLR2, TLR4, and TLR5) can activate integrin-dependent neutrophil adhesion. Moreover, the integrin α3β1 has been vitally implicated as a new player in neutrophil recruitment and TLR-mediated responses in septic inflammation. Furthermore, several endogenous inhibitory mechanisms of leukocyte recruitment have been identified, including the secreted molecules Del-1, PTX3, and GDF-15, which block distinct steps of the leukocyte adhesion cascade, as well as novel regulatory signaling pathways, involving the protein kinase AKT1 and IFN-λ2/IL-28A.
  
  
  CONCLUSIONS
  The leukocyte adhesion cascade is a tightly regulated process, subjected to both positive and negative regulators. Dysregulation of this process and hence neutrophil recruitment can lead to the development of inflammatory and autoimmune diseases.
authors.affiliation: aDepartment of Clinical Pathobiochemistry, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany bDepartment of Microbiology, Penn Dental Medicine, University of Pennsylvania, Philadelphia, USA *Pallavi Subramanian and Ioannis Mitroulis contributed equally to the writing of this article.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Subramanian
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000502:physiology*; D011485:Protein Binding; D019087:Selectins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000276:immunology
chemical_list: D018925:Chemokines; D039201:Integrin alpha3beta1; D019087:Selectins