Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

Table 1

Overview of some mechanisms that regulate extravasation of leukocyte subtypes in the order of events during the leukocyte extravasation cascade.

TEM step	Regulatory proteins	Cell	Function	Reference
Tethering/rolling/slow rolling	L-selectin, PSGL-1	EC/monos	L-selectin interacts with PNAd and PSGL-1 with P- and E-selectin to mediate proper rolling	[80]
	P-selectin, Mac1	EC/monos	Rolling and adhesion on ECM-bound platelets under flow	[84]
	P-selectin, PSGL-1, and CD44	EC/monos	Mediate rolling during monocyte recruitment to lymphoid tissues during inflammation	[79]
	CD44	Neutrophils/T cell	CD44 interacts with E-selectin in cooperation with PSGL-1 to mediate rolling	[141]
	TIM-1	T cell	TIM-1 interacts with PSGL-1 to mediate rolling	[140]
	CD43	T cell	CD43 interacts with E-selectin in cooperation with PSGL-1 to mediate rolling	[142, 143]
	P-selectin, PSGL1/PSGL-1 CD44, and L-selectin	ECs/neutrophils	Mediate rolling during recruitment of neutrophils in cremasteric postcapillary venules	[21, 22]
	PSGL-1, LFA-1/P-selectin, and ICAM-2	Neutrophil/ECs	Mediate sling formation and slow rolling	[32, 37]
Arrest/adhesion	VLA-4	Monos	PLC-, Ca-, and calmodulin-dependent arrest in response to chemokines	[86]
	VLA-4, GDF-15	Monos	GDF-15 reduces VLA-4 activation and monocyte adhesion	[87]
	LFA-1/ICAM-1	Neutrophils	Mediate neutrophil arrest	[42]
	EphA2	EC	Reduction of VCAM-1 expression and monocyte adhesion	[89]
	DARC	EC	CCL2 transport to the apical EC surface to induce monocyte activation and recruitment	[85]
	SIRPα/CD47	Monos/EC	Negatively regulates β2-integrin-mediated monocyte adhesion and transmigration	[91]
	CD47	T cell	Mediates integrin-dependent arrest on VCAM-1 and ICAM-1 and T cell recruitment in vivo	[145]
	Kindlin 3	T cell	Reinforces T cell adhesion	[146]
	CXCR4	Monos/B cell	CXCL12-dependent adhesion and diapedesis	[159]
	VCAM-1	B cell	VCAM-mediated arrest without rolling	[160]
Crawling	LFA-1, Mac1	Monos	Locomotion in search for the nearest suitable junction to start diapedesis	[92]
	LFA-1, Mac1	Monos	Crawling in unstimulated cremaster venules LFA-1-dependent that becomes Mac1-dependent after TNF-α-stimulation	[93]
	LFA-1; CCL3/CXC3CL1	Monos	Patrolling of resident monocytes and recruitment into noninflamed tissues	[72]
	Mac1/ICAM-1	Neutrophils	Control the luminal crawling of neutrophils on endothelial ICAM-1	[42]
	Mac1/ICAM-2	Neutrophils	Control the directionality and speed of crawling of neutrophils on endothelium	[45]
Cup formation	LFA-1/ICAM-1; VLA-4/VCAM-1; ALCAM-1	All	Clustering of these receptor-ligand pairs around adhering leukocytes causes GTPase activation, actin adaptor molecule recruitment, actin remodeling, and protrusion formation to engulf and support the adherent leukocyte	[49, 50, 94–100]
TEM	JAM-A, JAM-L, JAM-C, PECAM-1, DNAM-1, CD155, and CD99	All	Serve as counterreceptors for leukocyte-EC interactions during the passage through interendothelial cell contacts	[105, 108–112]
	Mac1, NE/JAM-C	Neutrophils/ECs	Control the directionality of neutrophil transendothelial migration. Cleavage of JAM-C induces aberrant transendothelial migration	[57]
	VAP-1	T cell	Together with ICAM-1 and CLEVER-1 specifically regulates T cell TEM	[156, 157]
		Monos	Support CX3CL1-dependent monocyte transmigration across hepatic sinusoidal EC	[161]
		Neutrophils	Blocking enzymatic activity of VAP-1 reduces neutrophil diapedesis and accumulation in lungs	[162, 163]
	Occludin	EC	Methamphetamine-induced Arp2/3 activation induces occludin internalization and monocyte transmigration	[113]
	JAM-A	Monos; Neutrophils	Blocking JAM-A interaction with LFA-1 reduces recruitment of monocytes and neutrophils into the brain after ischemia/reperfusion injury	[107]
After TEM	CXCL1/ICAM-1 Mac1/LFA-1	Pericytes/neutrophils	Abluminal crawling along pericyte processes	[63]
	VLA-3 VLA-6/collagen, laminin	Neutrophils/venular BM	Control the migration of neutrophils through venular basement membrane and exit through LERs	[10]
Interstitial motility	LFA-1; VLA-3	All	Interaction with abluminal ICAM-1 enables uropod extension while VLA-3 mediates movement of the leading edge in the BM	[68]
	ICAM-1	Pericytes	NG2^+-pericytes secrete chemokines and express ICAM-1 to attract/bind transmigrated leukocytes	[114]
	DDR1α	Monos	Expressed after transmigration in vivo to support migration within collagen-rich ECMs	[118]
	JAM-A	Neutrophils	Controls polarized interstitial migration	[55]
	RhoA	Monos	Active RhoA required for tail retraction to complete diapedesis	[115]