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Parietal and intravascular innate mechanisms of vascular inflammation.

Ramirez GA, Rovere-Querini P, Sabbadini MG, Manfredi AA - Arthritis Res. Ther. (2015)

Bottom Line: Here we discuss some recent advances in the effector and regulatory action of neutrophils and in the outcome of their interaction with circulating platelets.In parallel, we discuss novel insights into the role of humoral innate immunity in vascular inflammation.All these topics are discussed in light of potential clinical and therapeutic implications in the near future.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Ospedale San Raffaele, via Olgettina 60, 20132, Milan, Italy. ramirez.giuseppealvise@hsr.it.

ABSTRACT
Sustained inflammation of the vessel walls occurs in a large number of systemic diseases (ranging from atherosclerosis to systemic vasculitides, thrombotic microangiopathies and connective tissue diseases), which are ultimately characterized by ischemia and end-organ failure. Cellular and humoral innate immunity contribute to a common pathogenic background and comprise several potential targets for therapeutic intervention. Here we discuss some recent advances in the effector and regulatory action of neutrophils and in the outcome of their interaction with circulating platelets. In parallel, we discuss novel insights into the role of humoral innate immunity in vascular inflammation. All these topics are discussed in light of potential clinical and therapeutic implications in the near future.

No MeSH data available.


Related in: MedlinePlus

Checkpoints on leukocyte migration through inflamed vessels and tissues. In the setting of inflamed large arterial vessels, leukocytes adhere to the walls of the vasa vasorum and eventually extravasate through them. After accessing the adventitial layer of large arteries, leukocytes interact with vessel-residing dendritic cells that induce the generation of a follicle-like structure during chronic inflammation (A). In general, circulating leukocytes that approach an inflamed tissue (B) interact with signaling molecules expressed by activated endothelial cells (and platelets), which promote their adhesion to the vessel walls and eventually their migration through endothelial cells and perivascular connective tissue (1). This process mainly occurs at the level of postcapillary venules, where leukocytes are assisted by a first subset of neuron–glial antigen 2-negative/alpha-smooth muscle actin-positive (NG2− α-SMA+) pericytes (2). Both luminal and pericyte-derived signals enhance leukocyte survival and activation. As an example, neutrophils exposed to vascular cell adhesion molecule 1 (VCAM1) live longer: notably VCAM1 is required for the full development of anti-neutrophil cytoplasmic antibody-associated vasculitides glomerulonephritis, while its soluble and endothelial surface expression in rheumatoid arthritis correlates with joint damage and late-stage vascular injury, respectively. After diapedesis, leukocytes move through the interstitial space, mainly following slow and nonlinear routes. Interactions with a second subset of NG2+α-SMA+ arteriolar/capillary pericytes prompt leukocytes to progress faster and more linearly towards target tissues and might be involved in perpetuating vascular inflammation (3). CAM, cell adhesion molecules; vWF, von Willebrand factor.
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Fig1: Checkpoints on leukocyte migration through inflamed vessels and tissues. In the setting of inflamed large arterial vessels, leukocytes adhere to the walls of the vasa vasorum and eventually extravasate through them. After accessing the adventitial layer of large arteries, leukocytes interact with vessel-residing dendritic cells that induce the generation of a follicle-like structure during chronic inflammation (A). In general, circulating leukocytes that approach an inflamed tissue (B) interact with signaling molecules expressed by activated endothelial cells (and platelets), which promote their adhesion to the vessel walls and eventually their migration through endothelial cells and perivascular connective tissue (1). This process mainly occurs at the level of postcapillary venules, where leukocytes are assisted by a first subset of neuron–glial antigen 2-negative/alpha-smooth muscle actin-positive (NG2− α-SMA+) pericytes (2). Both luminal and pericyte-derived signals enhance leukocyte survival and activation. As an example, neutrophils exposed to vascular cell adhesion molecule 1 (VCAM1) live longer: notably VCAM1 is required for the full development of anti-neutrophil cytoplasmic antibody-associated vasculitides glomerulonephritis, while its soluble and endothelial surface expression in rheumatoid arthritis correlates with joint damage and late-stage vascular injury, respectively. After diapedesis, leukocytes move through the interstitial space, mainly following slow and nonlinear routes. Interactions with a second subset of NG2+α-SMA+ arteriolar/capillary pericytes prompt leukocytes to progress faster and more linearly towards target tissues and might be involved in perpetuating vascular inflammation (3). CAM, cell adhesion molecules; vWF, von Willebrand factor.

Mentions: Circulating leukocytes interact with cells that resides within the vessel walls as well as with other circulating cells that interact with blood vessels in order to gain information about ongoing damage in surrounding tissues and eventually to extravasate. To this purpose, either cells located in the lumen of blood vessels or cells located at the periphery of the vessel wall are able to productively interact with circulating and extravasating leukocytes and drive their subsequent effector responses. Cells that define the internal wall of blood vessels, such as the endothelium or the platelets recruited at sites of vessel injury to surrogate the function of the endothelium, indeed sense potential threats to the integrity of vessels and surrounding tissues through an array of pattern recognition receptors (PRR) [7,8]. After rapid mobilization of intracellular stores, endothelial cells and platelets expose a large array of signaling molecules such as P-selectin (from the endothelial and platelet side), vWF (from endothelial Weibel–Palade bodies) and inflammatory signals such as the high mobility group box 1 protein, the soluble form of CD40 ligand, leukotrienes LTA4 and LTB4 and tissue factor [7]. Later responses involve the transcriptionally regulated synthesis of E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecules (Figure 1B1).Figure 1


Parietal and intravascular innate mechanisms of vascular inflammation.

Ramirez GA, Rovere-Querini P, Sabbadini MG, Manfredi AA - Arthritis Res. Ther. (2015)

Checkpoints on leukocyte migration through inflamed vessels and tissues. In the setting of inflamed large arterial vessels, leukocytes adhere to the walls of the vasa vasorum and eventually extravasate through them. After accessing the adventitial layer of large arteries, leukocytes interact with vessel-residing dendritic cells that induce the generation of a follicle-like structure during chronic inflammation (A). In general, circulating leukocytes that approach an inflamed tissue (B) interact with signaling molecules expressed by activated endothelial cells (and platelets), which promote their adhesion to the vessel walls and eventually their migration through endothelial cells and perivascular connective tissue (1). This process mainly occurs at the level of postcapillary venules, where leukocytes are assisted by a first subset of neuron–glial antigen 2-negative/alpha-smooth muscle actin-positive (NG2− α-SMA+) pericytes (2). Both luminal and pericyte-derived signals enhance leukocyte survival and activation. As an example, neutrophils exposed to vascular cell adhesion molecule 1 (VCAM1) live longer: notably VCAM1 is required for the full development of anti-neutrophil cytoplasmic antibody-associated vasculitides glomerulonephritis, while its soluble and endothelial surface expression in rheumatoid arthritis correlates with joint damage and late-stage vascular injury, respectively. After diapedesis, leukocytes move through the interstitial space, mainly following slow and nonlinear routes. Interactions with a second subset of NG2+α-SMA+ arteriolar/capillary pericytes prompt leukocytes to progress faster and more linearly towards target tissues and might be involved in perpetuating vascular inflammation (3). CAM, cell adhesion molecules; vWF, von Willebrand factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308901&req=5

Fig1: Checkpoints on leukocyte migration through inflamed vessels and tissues. In the setting of inflamed large arterial vessels, leukocytes adhere to the walls of the vasa vasorum and eventually extravasate through them. After accessing the adventitial layer of large arteries, leukocytes interact with vessel-residing dendritic cells that induce the generation of a follicle-like structure during chronic inflammation (A). In general, circulating leukocytes that approach an inflamed tissue (B) interact with signaling molecules expressed by activated endothelial cells (and platelets), which promote their adhesion to the vessel walls and eventually their migration through endothelial cells and perivascular connective tissue (1). This process mainly occurs at the level of postcapillary venules, where leukocytes are assisted by a first subset of neuron–glial antigen 2-negative/alpha-smooth muscle actin-positive (NG2− α-SMA+) pericytes (2). Both luminal and pericyte-derived signals enhance leukocyte survival and activation. As an example, neutrophils exposed to vascular cell adhesion molecule 1 (VCAM1) live longer: notably VCAM1 is required for the full development of anti-neutrophil cytoplasmic antibody-associated vasculitides glomerulonephritis, while its soluble and endothelial surface expression in rheumatoid arthritis correlates with joint damage and late-stage vascular injury, respectively. After diapedesis, leukocytes move through the interstitial space, mainly following slow and nonlinear routes. Interactions with a second subset of NG2+α-SMA+ arteriolar/capillary pericytes prompt leukocytes to progress faster and more linearly towards target tissues and might be involved in perpetuating vascular inflammation (3). CAM, cell adhesion molecules; vWF, von Willebrand factor.
Mentions: Circulating leukocytes interact with cells that resides within the vessel walls as well as with other circulating cells that interact with blood vessels in order to gain information about ongoing damage in surrounding tissues and eventually to extravasate. To this purpose, either cells located in the lumen of blood vessels or cells located at the periphery of the vessel wall are able to productively interact with circulating and extravasating leukocytes and drive their subsequent effector responses. Cells that define the internal wall of blood vessels, such as the endothelium or the platelets recruited at sites of vessel injury to surrogate the function of the endothelium, indeed sense potential threats to the integrity of vessels and surrounding tissues through an array of pattern recognition receptors (PRR) [7,8]. After rapid mobilization of intracellular stores, endothelial cells and platelets expose a large array of signaling molecules such as P-selectin (from the endothelial and platelet side), vWF (from endothelial Weibel–Palade bodies) and inflammatory signals such as the high mobility group box 1 protein, the soluble form of CD40 ligand, leukotrienes LTA4 and LTB4 and tissue factor [7]. Later responses involve the transcriptionally regulated synthesis of E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecules (Figure 1B1).Figure 1

Bottom Line: Here we discuss some recent advances in the effector and regulatory action of neutrophils and in the outcome of their interaction with circulating platelets.In parallel, we discuss novel insights into the role of humoral innate immunity in vascular inflammation.All these topics are discussed in light of potential clinical and therapeutic implications in the near future.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Ospedale San Raffaele, via Olgettina 60, 20132, Milan, Italy. ramirez.giuseppealvise@hsr.it.

ABSTRACT
Sustained inflammation of the vessel walls occurs in a large number of systemic diseases (ranging from atherosclerosis to systemic vasculitides, thrombotic microangiopathies and connective tissue diseases), which are ultimately characterized by ischemia and end-organ failure. Cellular and humoral innate immunity contribute to a common pathogenic background and comprise several potential targets for therapeutic intervention. Here we discuss some recent advances in the effector and regulatory action of neutrophils and in the outcome of their interaction with circulating platelets. In parallel, we discuss novel insights into the role of humoral innate immunity in vascular inflammation. All these topics are discussed in light of potential clinical and therapeutic implications in the near future.

No MeSH data available.


Related in: MedlinePlus