Neutrophil Recruitment: From Model Systems to Tissue-Specific Patterns

Integrin activation for neutrophil extravasation into inflamed tissue is crucial only in certain tissues, because integrin independent recruitment can occur. Neutrophil integrins can exist in a bent-open headpiece conformation, which can hinder adhesion. Chemotactic cues guide neutrophils for extravasation, including differential chemokine CXCL1/CXCL2 gradients. Activation of the chemokine receptors CXCR2 and CXCR4 can impact neutrophil mobilization and clearance within bone marrow, similarly to mobilization of neutrophils from the marginated pool in the mouse lung. Neutrophils are ‘communicative’ cells, interacting with other cell populations to exert different functions that can depend on the tissue and/or stimulus. Neutrophil recruitment is not only vital for host defense, but also relevant in pathological inflammatory reactions, such as sepsis. Model systems have been established to examine different steps of the leukocyte recruitment cascade in vivo and in vitro under inflammatory conditions. Recently, tissue-specific recruitment patterns have come into focus, requiring modification of formerly generalized assumptions. Here, we summarize existing models of neutrophil recruitment and highlight recent discoveries in organ-specific recruitment patterns. New techniques show that previously stated assumptions of integrin activation and tissue invasion may need revision. Similarly, neutrophil recruitment to specific organs can rely on different organ properties, adhesion molecules, and chemokines. To advance our understanding of neutrophil recruitment, organ-specific intravital microscopy methods are needed. Neutrophil recruitment is not only vital for host defense, but also relevant in pathological inflammatory reactions, such as sepsis. Model systems have been established to examine different steps of the leukocyte recruitment cascade in vivo and in vitro under inflammatory conditions. Recently, tissue-specific recruitment patterns have come into focus, requiring modification of formerly generalized assumptions. Here, we summarize existing models of neutrophil recruitment and highlight recent discoveries in organ-specific recruitment patterns. New techniques show that previously stated assumptions of integrin activation and tissue invasion may need revision. Similarly, neutrophil recruitment to specific organs can rely on different organ properties, adhesion molecules, and chemokines. To advance our understanding of neutrophil recruitment, organ-specific intravital microscopy methods are needed. experimental animal model mimicking a bacterial infection in the abdominal cavity due to puncturing of the cecum and fecal contamination. influence on the motion direction of neutrophils, triggered by chemotactic cues, and which results in the directed migration of these cells mouse model used to mimic pathophysiological changes associated with MS. microfluidic devices used to examine cell interactions with specific substrates. cells flow within blood vessels without direct or constant endothelial interactions. Rheological and cellular properties lead to centralization of erythrocytes, whereas leukocytes are positioned towards the outer regions of the vessel diameter, termed ‘margination’. class of receptors, including CXCR2, crucial for neutrophil activation. Binding evolves in an intracellular signaling cascade, leading to chemokine-induced integrin activation. glycoprotein implicated in the proliferation of granulocytes and macrophages. contact site between two immune cells. utilized to image living tissue in animal models. It uses laser excitation with large wavelength photons resulting in reduced bleaching and improved penetration depth. one of the major integrins on neutrophils. It is a surface receptor capable of binding to ICAM-1 and can exist in different conformations. part of the outer membrane of Gram-negative bacteria; can be used for assays to mimic inflammatory responses against bacterial components. important integrin on the neutrophil surface. It binds preferably to fibrinogen yet is also capable of binding to ICAM proteins. Intravascular reservoir of neutrophils (e.g., in the lung). nonglycosylated heparin-binding chemokine. Small blood vessels collecting blood from capillaries in the microcirculation in the mouse cremaster muscle. DNA-containing networks released by neutrophils to entrap pathogens. here, reorganization of neutrophil intracellular components into one specific direction. form of sterile, fatty liver disease. inflammation of peritoneal cavity triggered by, for example, bacterial infection or Zymosan injection. 3D-oriented chemotactic gradient offering the distribution of chemokine concentration along its axes. relies on TIRF microscopy. Using cytoplasmic coloring or coloring of the plasma membrane leads to having fluorescent elements of the neutrophil outer membrane in close proximity (~200 nm) to the cover slip. The fluorescence intensity is then used to estimate and correlate the z-level intensity. remotely placed ischemic stimulus during a short time period; it is used to prime the organism for subsequent harmful challenges in other regions of the body. rate at which a displacement of the bloodstream layers appears. This can be calculated from centerline blood flow velocities. low-pressure fenestrated capillaries. exploits a physical phenomenon where light is reflected in light-transporting media, creating an evanescent wave of exponentially decreasing intensity within the bordering interface (glass versus cell); this leads to high-resolution fluorescence images in proximity to the cover slip.