The Physiology of Leukocyte Recruitment: An In Vivo Perspective

Petri, Bjӧrn; Phillipson, Mia; Kubes, Paul

doi:10.4049/jimmunol.180.10.6439

Cited by 233 publications

(219 citation statements)

References 96 publications

(97 reference statements)

Supporting

Mentioning

208

Contrasting

Unclassified

Order By: Relevance

“…Activation of endothelial cells during inflammatory responses is typically induced by proinflammatory cytokines, such as TNF-α and IL-1β (25), resulting in leukocyte recruitment at the sites of cellular damage. The process of leukocyte recruitment occurs through the expression of several adhesion molecules and chemokines such as MIF, which promotes the expression of endothelial P-selectin and arrest of leukocyte rolling (26); sICAM-1, which results in leukocyte adhesion (25); and MCP-1 and IL-8, which promote leukocyte emigration from the vasculature (27).…”

Section: Discussionmentioning

confidence: 99%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

View full text Add to dashboard Cite

Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

View full text Add to dashboard Cite

show abstract

“…P recise targeting of leukocytes to their marked battlegrounds is a key strategy for victory by the immune defense (1). Although this complex process has been a subject of intensive research for decades (2), many of the involved signaling pathways are still poorly understood (3).…”

Section: Integrin Regulation During Leukocyte Recruitmentmentioning

confidence: 99%

“…Although this complex process has been a subject of intensive research for decades (2), many of the involved signaling pathways are still poorly understood (3). Different sequential recruitment steps have been identified that each necessitates distinct functioning of particular members of the integrin family of adhesion molecules (1). These plasma membrane proteins feature a dual role of sensing and interacting with the surrounding environment (4).…”

Section: Integrin Regulation During Leukocyte Recruitmentmentioning

confidence: 99%

Integrin Regulation during Leukocyte Recruitment

Herter

Zarbock

2013

The Journal of Immunology

170

138

View full text Add to dashboard Cite

Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.

show abstract

“…This process requires that circulating leukocytes undergo a well-defined series of adhesion molecule-mediated interactions within the microvasculature at the site of inflammation (1,2). This sequence is typically initiated by selectin-mediated leukocyte rolling on the endothelial surface, followed by integrin-mediated arrest in response to chemoattractant-derived signals, and subsequent transmigration into tissues.…”

mentioning

confidence: 99%

Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion

Deane

Abeynaike

Norman

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Regulatory T cells (Tregs) must express appropriate skin-homing adhesion molecules to exert suppressive effects on dermal inflammation. However, the mechanisms whereby they control local inflammation remain unclear. In this study we used confocal intravital microscopy in wild-type and Foxp3-GFP mice to examine adhesion of effector T cells and Tregs in dermal venules. These experiments examined a two-challenge model of contact sensitivity (CS) in which Treg abundance in the skin progressively increases during the course of the response. Adhesion of CD4+ T cells increased during CS, peaking 8–24 h after an initial hapten challenge, and within 4 h of a second challenge. At these time points, 40% of adherent CD4+ T cells were Foxp3+ Tregs. CD4+ T cell adhesion was highly dependent on ICAM-1, and consistent with this finding, anti–ICAM-1 prevented Treg adhesion. Skin TGF-β levels were elevated in skin during both challenges, in parallel with Treg adhesion. In the two-challenge CS model, inhibition of ICAM-1 eliminated Treg adhesion, an effect associated with a significant increase in neutrophil adhesion. Similarly, total CD4+ T cell depletion caused an increase in adhesion of CD8+ T cells. Because Treg adhesion was restricted by both of these treatments, these experiments suggest that adherent Tregs can control adhesion of proinflammatory leukocytes in vivo. Moreover, the critical role of ICAM-1 in Treg adhesion provides a potential explanation for the exacerbation of inflammation reported in some studies of ICAM-1–deficient mice.

show abstract

The Physiology of Leukocyte Recruitment: An In Vivo Perspective

Cited by 233 publications

References 96 publications

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Integrin Regulation during Leukocyte Recruitment

Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion

Contact Info

Product

Resources

About