Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids

McDonald, Braedon; McAvoy, Erin F.; Lam, Florence; Gill, Varinder; Motte, Carol de la; Savani, Rashmin C.; Kubes, Paul

doi:10.1083/jcb1811oia3

Cited by 53 publications

(93 citation statements)

References 40 publications

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“…Several studies have shown a positive role of CD44 in inflammatory cell recruitment, 10,25,[36][37][38][39][40][41] whereas other investigations reported enhanced inflammatory cell migration in the absence of CD44. 8,9,24,35 This discrepancy is probably because of the differences in the cell type studied, the stimulus and organ involved, and the severity of the insult.…”

Section: Discussionmentioning

confidence: 98%

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Windt

Hoogendijk

Vos

et al. 2011

Laboratory Investigation

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Streptococcus pneumoniae is the most prevalent pathogen causing community-acquired pneumonia. CD44 is a transmembrane adhesion molecule, expressed by a wide variety of cell types, that has several functions in innate and adaptive immune responses. In this study, we tested the hypothesis that CD44 is involved in the host response during pneumococcal pneumonia. On intranasal infection with a lethal dose of S. pneumoniae CD44-knockout (KO) mice showed a prolonged survival when compared with wild-type mice, which was accompanied by a diminished pulmonary bacterial growth and reduced dissemination to distant body sites. Whereas, proinflammatory cytokine responses and lung pathology were not affected, CD44 deficiency resulted in increased early neutrophil influx into the lung. In separate experiments, we confirmed a detrimental role of CD44 in host defense against pneumococci during sublethal pneumonia, as demonstrated by an improved capacity of CD44 KO mice to clear a low infectious dose. In addition, CD44 appeared important for the resolution of lung inflammation during sublethal pneumonia, as shown by histopathology of lung tissue slides. In conclusion, we show here that CD44 facilitates bacterial outgrowth and dissemination during pneumococcal pneumonia, which in lethal infection results in a prolonged survival of CD44 KO mice. Moreover, during sublethal pneumonia CD44 contributes to the resolution of the inflammatory response.

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Section: Discussionmentioning

confidence: 98%

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Windt

Hoogendijk

Vos

et al. 2011

Laboratory Investigation

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“…To assess a role for the CD44/ hyaluronan pathway, mice were treated with hyaluronidase (20 U/g, i.v. ; Sigma-Aldrich) 4 h prior to imaging (37). In these experiments, mice also received Abs against ICAM-1 and the a 4 integrin to assess the effect of combined inhibition of these pathways.…”

Section: Experimental Protocolmentioning

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

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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.

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“…Adherent leukocytes were defined as leukocytes that remained stationary on the venular or sinusoidal endothelium for 30 sec or longer, as previously described. 34,35 Under white-light trans-illumination, leukocytes can be clearly visualized within the vasculature. The numbers of adherent cells within the vessels were counted using video playback analysis of each experiment, and are expressed as the number of adherent leukocytes per 100 lm in postsinusoidal venules or per field of view in sinusoids.…”

Section: Fluorescence Intravital Microscopy Of the Liver (Surgery)mentioning

confidence: 99%

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

McDonald

Spicer

Giannais

et al. 2009

Intl Journal of Cancer

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204

163

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Interactions between endothelial selectins and selectin ligands expressed on tumor cells have been implicated in the binding of circulating metastatic cancer cells to the vascular endothelium during extravasation. Moreover, there is mounting evidence that inflammatory environments can accelerate the progression of metastasis by neutrophil mediated mechanisms. In this study, a physiologically relevant in vivo model of early metastasis coupled with intravital microscopy was used to visualize the trafficking of tumor cells within the liver vasculature in real time. Using GFPlabeled Lewis lung carcinoma subline H-59 cells, we show here that disrupting the interactions between endothelial selectins and tumor cell selectin ligands diminished tumor cell recruitment to the liver. Furthermore, systemic inflammation induced by intravenous injection of lipopolysaccharide significantly enhanced the metastatic potential of these lung carcinoma cells by increasing their propensity to adhere to the liver sinusoidal endothelium. Confocal microscopy revealed frequent colocalization of cancer cells with neutrophils and neutrophil depletion in vivo significantly attenuated the lipopolysaccharide-induced increase in H-59 cell adhesion. Although direct selectin-selectin ligand interactions contributed significantly to tumor cell adhesion to sinusoidal endothelial cells, we show here that in addition, interactions between adherent neutrophils within the inflamed sinusoids and circulating tumor cells may further increase tumor cell arrest in the liver. ' 2009 UICC Key words: cancer; metastasis; lung; rodent; adhesion molecules; e-selectin; neutrophil; sialyl Lewis X Lung cancer is the leading cause of cancer-related deaths worldwide. 1 A high proportion of patients harbor metastasis to regional lymph nodes upon presentation, and over half of all patients who undergo curative intent surgical resection of the lung will develop metastatic recurrence. 2 The liver is a common site of metastasis for lung cancer, with autopsy studies showing hepatic metastases in over 50% of lung cancer patients. 3 The hematogenous dissemination of cancer cells from a primary tumor to distant organs involves a cascade of sequential steps (reviewed in Refs. 4,5). The adhesion of circulating tumor cells to the vascular endothelium of distant organs is a key step in the metastatic cascade that may determine the organ tropism and extent of metastasis. Interactions between endothelial selectins and tumor cell selectin ligands have been implicated in the metastatic process. [5][6][7][8] Selectins are a family of transmembrane glycoproteins possessing an extracellular lectin domain that binds to carbohydrate moieties present on their ligands. 9 The three known selectins that function as cell adhesion molecules are expressed on the surface of endothelial cells (E-selectin and P-selectin), platelets (P-selectin) and leukocytes (L-selectin). E-selectin has been shown to contribute to the metastatic spread of multiple cancers, including lung and colon carcinoma, and m...

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Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids

Cited by 53 publications

References 40 publications

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

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

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

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