Tissue-Specific Neutrophil Recruitment into the Lung, Liver, and Kidney

Rossaint, Jan; Zarbock, Alexander

doi:10.1159/000345943

Cited by 91 publications

(84 citation statements)

References 89 publications

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“…These data are in contrast to a previous report that indicates that CD45 do not have a prominent function in neutrophil recruitment in a S. aureus airpouch model (12). These data support the hypothesis that the molecular mechanisms of neutrophil recruitment into different tissues differ (45). Another explanation for these controversial results is that different bacteria elicit distinctive signaling pathways (35).…”

Section: Discussionsupporting

confidence: 49%

Mutation in the CD45 Inhibitory Wedge Modulates Integrin Activation and Leukocyte Recruitment during Inflammation

Germena

Volmering

Sohlbach

et al. 2015

The Journal of Immunology

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Neutrophil recruitment to the site of inflammation plays a pivotal role in host defense. Src family kinases (SFKs) activation is required for integrin and chemokine signaling as well as immune cell function. The receptor-like protein tyrosine phosphatase CD45 positively regulates chemoattractant signaling acting on SFK activity. To further investigate the role of CD45 in neutrophil recruitment and function, we analyzed transgenic mice carrying a single point mutation (CD45E613R), which constitutively activates CD45. By using intravital microscopy experiments, we demonstrated that different steps of the leukocyte recruitment cascade were affected in CD45E613R mutant mice. The rolling velocity of CD45E613R mutant neutrophils was decreased compared with wild-type neutrophils that subsequently resulted in an increased number of adherent cells. The analysis of β2 integrins LFA-1 and macrophage-1 Ag (Mac-1) showed that in CD45E613R mutant neutrophils LFA-1 adhesiveness was impaired, and avidity was enhanced, whereas Mac-1 adhesiveness was increased. Because of the increased Mac-1 adhesiveness, neutrophil crawling was impaired in CD45E613R mutant compared with wild-type neutrophils. In an Escherichia coli lung infection model, CD45E613R mice displayed a decreased neutrophil recruitment into the alveolar compartment, which resulted in an increased number of CFUs in the lung. Our data demonstrate that the CD45E613R mutation modulates integrin activation and leukocyte recruitment during inflammation.

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Section: Discussionsupporting

confidence: 49%

Mutation in the CD45 Inhibitory Wedge Modulates Integrin Activation and Leukocyte Recruitment during Inflammation

Germena

Volmering

Sohlbach

et al. 2015

The Journal of Immunology

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“…the leukocytes leave the vessel and migrate into the inflamed tissue [14]. Recent studies demonstrated that leukocyte recruitment into the kidney occurs at two different sites [16]: Leukocyte rolling and recruitment in the postcapillary venules in the cortex are E-selectin-dependent [17], whereas glomerular inflammation results in an increase in the duration of retention of static and migrating leukocytes [18]. …”

Section: Introductionmentioning

confidence: 99%

Adhesion Molecules Involved in Neutrophil Recruitment during Sepsis-Induced Acute Kidney Injury

Herter

Rossaint²,

Spieker³

et al. 2014

J Innate Immun

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Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two β₂-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of β₂-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.

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“…Due to its unique microvasculature, the molecular mechanisms involved in neutrophil recruitment into the lung differ compared with other organs (51). Chemokine signaling plays a dominant role for neutrophil recruitment into the lung tissue, whereas selectins are only of minor importance in response to most inflammatory stimuli in the lung.…”

Section: Discussionmentioning

confidence: 99%

Lidocaine Reduces Neutrophil Recruitment by Abolishing Chemokine-Induced Arrest and Transendothelial Migration in Septic Patients

Berger

Rossaint

Aken

et al. 2014

The Journal of Immunology

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The inappropriate activation, positioning, and recruitment of leukocytes are implicated in the pathogenesis of multiple organ failure in sepsis. Although the local anesthetic lidocaine modulates inflammatory processes, the effects of lidocaine in sepsis are still unknown. This double-blinded, prospective, randomized clinical trial was conducted to investigate the effect of lidocaine on leukocyte recruitment in septic patients. Fourteen septic patients were randomized to receive either a placebo (n = 7) or a lidocaine (n = 7) bolus (1.5 mg/kg), followed by continuous infusion (100 mg/h for patients >70 kg or 70 mg/h for patients <70 kg) over a period of 48 h. Selectin-mediated slow rolling, chemokine-induced arrest, and transmigration were investigated by using flow chamber and transmigration assays. Lidocaine treatment abrogated chemokine-induced neutrophil arrest and significantly impaired neutrophil transmigration through endothelial cells by inhibition of the protein kinase C-θ while not affecting the selectin-mediated slow leukocyte rolling. The observed results were not attributable to changes in surface expression of adhesion molecules or selectin-mediated capturing capacity, indicating a direct effect of lidocaine on signal transduction in neutrophils. These data suggest that lidocaine selectively inhibits chemokine-induced arrest and transmigration of neutrophils by inhibition of protein kinase C-θ while not affecting selectin-mediated slow rolling. These findings may implicate a possible therapeutic role for lidocaine in decreasing the inappropriate activation, positioning, and recruitment of leukocytes during sepsis.

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Tissue-Specific Neutrophil Recruitment into the Lung, Liver, and Kidney

Cited by 91 publications

References 89 publications

Mutation in the CD45 Inhibitory Wedge Modulates Integrin Activation and Leukocyte Recruitment during Inflammation

Mutation in the CD45 Inhibitory Wedge Modulates Integrin Activation and Leukocyte Recruitment during Inflammation

Adhesion Molecules Involved in Neutrophil Recruitment during Sepsis-Induced Acute Kidney Injury

Lidocaine Reduces Neutrophil Recruitment by Abolishing Chemokine-Induced Arrest and Transendothelial Migration in Septic Patients

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