Overlapping Roles of Endothelial Selectins and Vascular Cell Adhesion Molecule-1 in Immune Complex-Induced Leukocyte Recruitment in the Cremasteric Microvasculature

Norman, M. Ursula; Velde, Nicholas C. van de; Timoshanko, Jennifer R.; Issekutz, Andrew C.; Hickey, Michael J.

doi:10.1016/s0002-9440(10)63506-7

Cited by 36 publications

(56 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To examine the effect of selectin blockade, RB40.34 (anti-P-selectin; 20 mg, BD Biosciences) and RME-1 (anti-E-selectin, 100 mg; generously provided by Dr. Andrew Issekutz, Dalhousie University, Halifax, NS, Canada) were administered i.v. 15 min before challenge (23). Control mice received the same amount of nonspecific IgG.…”

Section: Experimental Protocolmentioning

confidence: 99%

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Chow

Mueller

Deane

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. Here we used multiphoton imaging in Foxp3‐GFP mice to examine the behavior of endogenous Tregs in skin. While Tregs were readily detectable in the uninflamed dermis, most were non‐motile. Induction of contact sensitivity increased the proportion of motile Tregs, as well as inducing Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, and by inhibition of effector cell recruitment, indicating a role for T cell‐dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naïve mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4+ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4+ effector cells, in that only a low proportion of Tregs are migratory under resting conditions. However, during inflammation the proportion of migratory Tregs increases, raising the possibility that this response may be important in controlling skin inflammation.

show abstract

Section: Experimental Protocolmentioning

confidence: 99%

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Chow

Mueller

Deane

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Neutrophils were observed by epi-illumination at 450 -490 nm, using a 515-nm emission filter. In additional experiments, interactions of isolated neutrophils were examined in postcapillary venules of the cremaster muscle, prepared for intravital microscopy as described previously (31). In these experiments, an inflammatory response was established in the cremaster muscle by prior local injection of TNF (50 ng, 4 h), then neutrophils were delivered to the cremasteric microvasculature via a catheter inserted retrogradely in the femoral artery.…”

Section: Analysis Of Leukocyte Interactions Within Glomerulimentioning

confidence: 99%

Leukocyte Recruitment to the Inflamed Glomerulus: A Critical Role for Platelet-Derived P-Selectin in the Absence of Rolling

Kuligowski

Kitching

Hickey

2006

The Journal of Immunology

Self Cite

122

153

View full text Add to dashboard Cite

The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of directly visualizing the glomerulus, the mechanisms of leukocyte recruitment to glomerular capillaries are poorly understood. To overcome this, we rendered murine kidneys hydronephrotic to allow the visualization of the functional glomerular microvasculature during an inflammatory response. These experiments demonstrated that following infusion of anti-glomerular basement membrane (GBM) Ab, leukocytes became adherent in glomerular capillaries via a process of immediate arrest, without undergoing prior detectable rolling. However, despite the absence of rolling, this recruitment involved nonredundant roles for the P-selectin/P-selectin glycoprotein ligand-1 and β2 integrin/ICAM-1 pathways, suggesting that a novel form of the multistep leukocyte adhesion cascade occurs in these vessels. Anti-GBM Ab also increased glomerular P-selectin expression and induced a P-selectin-independent increase in platelet accumulation. Moreover, platelet depletion prevented both the increase in glomerular P-selectin, and the leukocyte recruitment induced by anti-GBM Ab. Furthermore, depletion of neutrophils and platelets also prevented the increase in urinary protein excretion induced by anti-GBM Ab, indicating that their accumulation in glomeruli contributed to the development of renal injury. Finally, infusion of wild-type platelets into P-selectin-deficient mice restored the ability of glomeruli in these mice to support leukocyte adhesion. Together, these data indicate that anti-GBM Ab-induced leukocyte adhesion in glomeruli occurs via a novel pathway involving a nonrolling interaction mediated by platelet-derived P-selectin.

show abstract

“…We selected 1-3 venules (25-40 m in diameter) for recording in each experiment. Leukocyte rolling flux, rolling velocity, adhesion, and emigration as well as the venular diameter (Dv) were quantitated off-line using playback analysis, as previously described (28,29). The centerline red blood cell (RBC) velocity (V RBC ) in the vessel was measured with an optical Doppler velocimeter (Microcirculation Research Institute, Texas A&M University, College Station, TX), and the mean RBC velocity (V mean ) was determined as the V RBC /1.6.…”

Section: Animals Mifmentioning

confidence: 99%

“…P-selectin expression in the cremaster muscles of LPS-treated wild-type and MIF Ϫ/Ϫ mice was quantitated as previously described (29). Briefly, Alexa 488-conjugated RMP-1 (detected via epiillumination at 450-490 nm, with a 515-nm emission filter) was used to label P-selectin, and Alexa 594-conjugated anti-KLH mAb (detected using a 530-585-nm excitation filter, with a 615-nm emission filter) was used as a nonspecific control IgG.…”

Section: Animals Mifmentioning

confidence: 99%

See 1 more Smart Citation

Reduced leukocyte–endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor–deficient mice

Gregory¹,

Leech²,

David³

et al. 2004

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with established roles in a range of inflammatory conditions. However, it is not known whether MIF influences inflammation via the direct promotion of leukocyteendothelial cell interactions. Therefore, the aim of these experiments was to investigate the ability of MIF to regulate leukocyte-endothelial cell interactions in the inflamed microvasculature.Methods. Intravital microscopy was used to examine postcapillary venules in the cremaster muscle and synovium of wild-type and MIF ؊/؊ mice. Leukocyte-endothelial cell interactions (rolling, adhesion, emigration) were compared under a range of inflammatory conditions.Results. In cremasteric postcapillary venules of MIF ؊/؊ mice, lipopolysaccharide (LPS)-induced leukocyte rolling, adhesion, and emigration were significantly reduced relative to that in wild-type mice. Similar responses were observed in response to tumor necrosis factor ␣ and histamine. Examination of the synovial microvasculature following exposure to carrageenan revealed that leukocyte rolling and adhesion in synovial postcapillary venules and leukocyte entry into the joint space were also reduced significantly in MIF ؊/؊ mice. In each of these models, the level of P-selectindependent rolling was reduced in MIF ؊/؊ mice. Despite this, no difference in P-selectin expression was observed following LPS treatment. However, microvascular shear forces were elevated in MIF ؊/؊ mice, raising a possible mechanism to explain the reduced interactions in these animals.Conclusion. MIF ؊/؊ mice consistently displayed a reduction in P-selectin-dependent rolling, suggesting that MIF exerts proinflammatory effects, in part, via the promotion of P-selectin-mediated rolling. Together, these data indicate that MIF promotes interactions between leukocytes and endothelial cells, thereby enhancing the entry of leukocytes into sites of inflammation.

show abstract

Overlapping Roles of Endothelial Selectins and Vascular Cell Adhesion Molecule-1 in Immune Complex-Induced Leukocyte Recruitment in the Cremasteric Microvasculature

Cited by 36 publications

References 47 publications

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Leukocyte Recruitment to the Inflamed Glomerulus: A Critical Role for Platelet-Derived P-Selectin in the Absence of Rolling

Reduced leukocyte–endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor–deficient mice

Contact Info

Product

Resources

About