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. 2018 Nov 27;9:2739. doi: 10.3389/fimmu.2018.02739

Figure 4.

Figure 4

Kidney: the neutrophil actions in different capillary beds. (A) Tethering and adhesion/retention of neutrophils in the glomeruli. (1) In the glomeruli P-selectin is required for neutrophils recruitment. As neutrophils do not express this molecule, P-selectin has to be provided by other sources, such as platelets. Platelets adhere to the endothelium, in a GPVI and αIIbβ3/fibrinogen/ICAM-1-dependent fashion, and neutrophils are thereafter recruited by interaction of leukocytic PSGL-1 with P-selectin. (2) Upon acute inflammation, neutrophils have been found to be retained in the vasculature for increased periods of time (also referred to as “dwell time”), via Mac-1-β2-integrins interaction. Whether this “dwell time” is preceded or followed by P-selectin-dependent tethering remains to be described. (3) Neutrophils retained in the endothelium by Mac-1-β2-integrins interaction release ROS upon activation, which in turn increases Mac-1 expression and consequently expands the cell adhesion times. (4) Neutrophil “dwell time,” recruitment and ROS production can also be fostered by patrolling monocytes due to release of TNF or direct interaction with the neutrophil. (B) Neutrophil recruitment in the peritubular capillaries. (1) In the peritubular capillaries, neutrophil recruitment is initiated by ICAM-1, P- and E- selectin interactions. (2) Neutrophils can, however, also be recruited in a CD44-HA dependent manner. Under homeostatic conditions, CD44 is poorly expressed by ECs, but upon injury its expression strongly increases. (3) Neutrophil transmigration is assisted by pericytes, which express VAP-1 that generates a local hydrogen peroxide gradient, guiding the neutrophil to the TEM site. (4) In addition, migrating neutrophils release cytokines that further guide other neutrophils and induce vascular permeability facilitating the extravasation. EC, Endothelial cell; GPVI, Glycoprotein VI; HA, Hyaluronic acid; HP, Hydrogen peroxide; ICAM-1, Intercellular adhesion molecule 1; Mac-1, Macrophage-1 antigen; PSGL-1, P-selectin glycoprotein ligand 1; ROS, Reactive oxygen species; SHAP, Serum-derived hyaluronan-associated protein; TEM, Transendothelial migration; VAP-1, Vascular adhesion protein.