an uncontrolled stage, where white blood neutrophils begin destroying host tissues at unprecedented rates, claiming the lives of about 200,000 people in the united states alone. neutrophil dysfunction is usually preceded by an infection of some sort, which triggers pathogen-associated molecular patterns (pamp). as leukocyte extravasation intensifies, more tissues are damaged by neutrophils, which release oxygen radicals and proteases. recent studies with synvivo synthetic microvascular network (smn) made it possible to study anti-inflammatory therapeutics to treat pathologies caused by neutrophil dysfunction. the smn enables the thorough analysis of each stage of leukocyte extravasation, thereby providing a methodology to quantify the effect of the drug in impeding leukocyte extravasation. some of the recent findings demonstrate the effect of hydrodynamics on neutrophil-endothelial interactions. in other words, adhesion of neutrophils is heavily impacted by shear forces as well as molecular interactions. moreover, as shear rate decreases (e.g., in post-capillary venules), immobilization of the leukocytes becomes easier and thus, more prevalent. the opposite is also true; vessels in which shear forces are high render the immobilization of the leukocytes more difficult. this has high implications in various diseases, where disruptions in blood flow gravely impact immune system response by impeding or expediting the immobilization of the leukocytes. having this knowledge allows for better studies of the effect of drugs on leukocyte extravasation. footnotes monk pn, scola am, madala p, fairlie dp (october 2007). "function, structure and therapeutic potential of complement c5a receptors". british journal of pharmacology. 152 (4): 429–48. doi:10.1038/sj.bjp.0707332. pmc 2050825. pmid 17603557. maverakis e, kim k, shimoda m, gershwin me, patel f, wilken r, raychaudhuri s, ruhaak lr, lebrilla cb (february 2015). "glycans in the immune system and the altered glycan theory of autoimmunity: a critical review". journal of autoimmunity. 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. pmc 4340844. pmid 25578468. beekhuizen, henry; furth, ralph van (1998). "diapedesis". encyclopedia of immunology. pp. 757–760. doi:10.1006/rwei.1999.0200. isbn 978-0-12-226765-9. escribano j, chen mb, moeendarbary e, cao x, shenoy v, garcia-aznar jm, et al. (may 2019). "balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation". plos computational biology. 15 (5): e1006395. arxiv:1811.09326. bibcode:2019plscb..15e6395e. doi:10.1371/journal.pcbi.1006395. pmc 6497229. pmid 31048903. sorokin l (october 2010). "the impact of the extracellular matrix on inflammation". nature reviews. immunology. nature publishing group. 10 (10): 712–23. doi:10.1038/nri2852. pmid 20865019. s2cid 18130467. mcever rp, beckstead jh, moore kl, marshall-carlson l, bainton df (july 1989). "gmp-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in weibel-palade bodies". the journal of clinical investigation. 84 (1): 92–9. doi:10.1172/jci114175. pmc 303957. pmid 2472431. anderson ao, anderson nd (november 1976). "lymphocyte emigration from high endothelial venules in rat lymph nodes". immunology. 31 (5): 731–48. pmc 1445135. pmid 992709. wiese g, barthel sr, dimitroff cj (february 2009). "analysis of physiologic e-selectin-mediated leukocyte rolling on microvascular endothelium". journal of visualized experiments. 24 (24): 1009. doi:10.3791/1009. pmc 2730781. pmid 19229187. thomas we, nilsson lm, forero m, sokurenko ev, vogel v (september 2004). "shear-dependent 'stick-and-roll' adhesion of type 1 fimbriated escherichia coli". molecular microbiology. 53 (5): 1545–57. doi:10.1111/j.1365-2958.2004.04226.x. pmid 15387828. s2cid 24777923. yago t, wu j, wey cd, klopocki ag, zhu c, mcever rp (september 2004). "catch bonds govern adhesion through l-selectin at threshold shear". the journal of cell biology. 166 (6): 913–23. doi:10.1083/jcb.200403144. pmc 2172126. pmid 15364963. thomas we, trintchina e, forero m, vogel v, sokurenko ev (june 2002). "bacterial adhesion to target cells enhanced by shear force". cell. 109 (7): 913–23. doi:10.1016/s0092-8674(02)00796-1. pmid 12110187. nabel g, baltimore d (1987). "an inducible transcription factor activates expression of human immunodeficiency virus in t cells". nature. 326 (6114): 711–3. bibcode:1987natur.326..711n. doi:10.1038/326711a0. pmid 3031512. s2cid 4317942. prabhakarpandian b, shen mc, pant k, kiani mf (november 2011). "microfluidic devices for modeling cell-cell and particle-cell interactions in the microvasculature". microvascular research. 82 (3): 210–20. doi:10.1016/j.mvr.2011.06.013. pmc 3215799. pmid 21763328. smith am, prabhakarpandian b, pant k (may 2014). "generation of shear adhesion map using synvivo synthetic microvascular networks". journal of visualized experiments. 87 (87): e51025. doi:10.3791/51025. pmc 4207183. pmid 24893648. lamberti g, prabhakarpandian b, garson c, smith a, pant k, wang b, kiani mf (august 2014). "bioinspired microfluidic assay for in vitro modeling of leukocyte-endothelium interactions". analytical chemistry. 86 (16): 8344–51. doi:10.1021/ac5018716. pmc 4139165. pmid 25135319. soroush f, zhang t, king dj, tang y, deosarkar s, prabhakarpandian b, kilpatrick le, kiani mf (november 2016). "a novel microfluidic assay reveals a key role for protein kinase c δ in regulating human neutrophil-endothelium interaction". journal of leukocyte biology. 100 (5): 1027–1035. doi:10.1189/jlb.3ma0216-087r. pmc 5069089. pmid 27190303.