Neutrophil Chemotaxis

Chemotaxis, the guided movement of cells by chemical gradients created by chemoattractant proteins, such as chemokines and bacterial products produced at the site of inflammation, probably emerged early in eukaryotic evolution {Kay, 2008 #3289}. Neutrophils are highly mobile cells that readily undergo chemotaxis. Neutrophils can detect as low as 1/100th of a chemokine gradient. They polarize their migration towards bacterial peptides over a pool of other chemical gradients to reach sites of inflammation. Neutrophils adopt a ‘pseudopodia- centered model’ to migrate towards the chemical gradient. Neutrophils undergo amoeboid-type movement, the most primitive form of single cell migration. Amoeboid-type of cell migration is characterized by rapid
Chemokine distribution is concentration-dependent and, eventually, creates an intravascular chemokine gradient for neutrophil chemotaxis. Neutrophil chemotaxis begins with the phosphorylation and activation of specific G- protein coupled chemokine receptors on the neutrophil surface, which will result in a conformational change of surface integrin proteins. Binding between LFA proteins on neutrophil surface and ICAMs of endothelium induces a conformational change to talin-1, a cytoskeletal protein, leading to firm attachment and slow rolling of neutrophil {Wang, 2011
Along with ICAMs and integrins, neutrophils require adhesion molecules like vascular cell adhesion protein-1 (VCAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), CD99, vascular adhesion protein 1(VAP1), and leukocyte specific protein 1 (LSP1) to cross the endothelial barrier {Li Jeon, 2002 #3206}. Neutrophils migrate to tissue spaces either between two endothelial cells (paracellular) or through an endothelial cell (transcellular). Paracellular migration requires relaxation of endothelial cell junctions and is the most common mode of neutrophil migration. During transcellular migration, endothelial cells form ‘domes’ around adhered neutrophils by extending villi-like projections {Parkos, 1992 #3361}. Domes are rich in ICAM1 and VCAM1, which actively interact with LFA-1 and integrin α4 (VLA4; very late antigen 4) of neutrophils. LSP1, an actin binding protein expressed abundantly in endothelial cytoplasm and nucleus, regulates endothelial cell dome formation. This process is completely different from endocytosis because neutrophils never interact with the intracellular compartment of endothelium {Halilovic, 2015