Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade

By M. Phillipson, B. Heit, P. Colarusso, Lixin Liu, Christie M. Ballantyne, P. Kubes. Journal of Experimental Medicine, 2006

745 citations recorded by the source corpus.

The prevailing view is that the β2-integrins Mac-1 (αMβ2, CD11b/CD18) and LFA-1 (αLβ2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1−/− mice but very little adhesion in LFA-1−/− mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1−/− neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1−/− neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1−/− cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1–dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1–dependent adhesion followed by Mac-1–dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.

Subfields: Hematology, Immunology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/6d91294fed7be050fafdea2cb9fd5dea4a79ac5e

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Citations in the corpus

Neutrophils, from marrow to microbes. (2010, background): “LFA-1 is the principal adhesion molecule on neutrophils that mediates transition from rolling to adhesion on the endothelial cell surface (Phillipson et al., 2006).”
Mechanisms of Leukocyte Transendothelial Migration (2011, background): “(92) reported that neutrophils deficient in CD11b/CD18 adhere to the endothelium at a site of inflammation but transmigrate poorly due to their inability to locomote along the endothelial surface.”
Orchestrating the orchestrators: chemokines in control of T cell traffic (2008, background): “Junctional diapedesis requires the migration of leukocytes from sites of firm arrest to nearby bi- or tricellular junctions of the endothelium and, indeed, lumenal 'crawling' of innate leukocyte populations in vivo has been shown by intravital microscop”
The neutrophil in vascular inflammation (2011, background): “In CD11b-deficient mice, neutrophils did not crawl within the vasculature, and, consequently, transcellular transmigration through endothelial cells predominated 5 .”
Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment (2019, background): “This is followed by cell spreading, Mac-1-mediated crawling (62), paracellular or transcellular extravasation, and migration into lymph nodes or tissues.”
Reactive Oxygen Species in Inflammation and Tissue Injury (2014, positive): “Mac-1 also binds to ICAM-1 and mediates crawling of neutrophils along endothelial cells to the entry of endothelial junctions for paracellular migration (350).”
The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. (2016, background): “phage-1 antigen (Mac1), with endothelial intercellular adhesion molecules is essential for firm adhesion.(144) Neutrophil”
Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. (2018, background): “thus mediating adhesion to the endothelial cell surface [188]; Mac-1 also binds to ICAM-1 and mediates crawling of neutrophils [188].”