Keratocan and Lumican Regulate Neutrophil Infiltration and Corneal Clarity in Lipopolysaccharide-induced Keratitis by Direct Interaction with CXCL1

Carlson, Eric C.; Lin, Michelle; Liu, Chia-Yang; Kao, Winston W.‐Y.; Pérez, Víctor L.; Pearlman, Eric

doi:10.1074/jbc.m705823200

Cited by 68 publications

(72 citation statements)

References 25 publications

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“…Recent studies using chimeric mice have demonstrated that waves of bone marrow-derived cells invade the cornea in the first few days after epithelial scrape or other corneal injury in the mouse (Wilson et al, 2004;Carlson et al, 2006Carlson et al, , 2007. However, studies have also demonstrated that there are resident CD11b-positive cells present in the unwounded corneal stroma (Mayer et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Stapleton

Chaurasia

Medeiros

et al. 2008

Experimental Eye Research

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Interleukin (IL)-1α and β are important modulators of many functions of corneal epithelial and stromal cells that occur following injury to the cornea, including the influx of bone marrow-derived inflammatory cells into the stroma attracted by chemokines released from the stroma and epithelium. In this study, we examined the effect of topical soluble IL-1 receptor antagonist on bone marrowderived cell influx following corneal epithelial scrape injury in a mouse model. C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1 receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20 mg/ml or vehicle for 24 h prior to immunocytochemical detection of marker CD11b-positive cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a marked effect in blocking cell influx. For example, in experiment 1, topical IL-1 receptor antagonist markedly reduced detectible CD11b-positive cells into the corneal stroma at 24 h after epithelial injury compared with the vehicle control (3.5 ± 0.5 (standard error of the mean) cells/400× field and 13.9 ± 1.2 cells/400× field, respectively, p < 0.01). A second experiment with a different observer performing cell counting had the same result. Thus, the data demonstrate conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b-positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor antagonist could be an effective adjuvant for clinical treatment of corneal conditions in which unwanted inflammation has a role in the pathophysiology of the disorder.

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Section: Discussionmentioning

confidence: 99%

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Stapleton

Chaurasia

Medeiros

et al. 2008

Experimental Eye Research

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“…Lumican facilitates innate immune response by binding LPS and CD14, the glycerol phosphatidylinositol-linked cell surface adaptor protein that transfers the LPS signal to toll-like receptor 4 (18). In a corneal injury model neutrophil influx is delayed in the Lum Ϫ/Ϫ mice (19,20). Although this may be partly due to impaired innate immune response, it raises the possibility that lumican may have an additional role in neutrophil migration.…”

mentioning

confidence: 82%

Extracellular Matrix Lumican Deposited on the Surface of Neutrophils Promotes Migration by Binding to β2 Integrin

Lee¹,

Bowrin²,

Hamad

et al. 2009

Journal of Biological Chemistry

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) and LFA-1 (␣ L / ␤ 2 ), the two major PMN surface integrins. We detected lumican on the surface of peritoneal PMNs and not bone marrow or peripheral blood PMNs. This suggests that PMNs must acquire lumican during or after crossing the endothelial barrier as they exit circulation. We also found that peritoneal PMNs do not express lumican, whereas endothelial cells do. Taken together these observations suggest a novel endothelial lumican-mediated paracrine regulation of neutrophils early on in their migration path.Polymorphonuclear neutrophils (PMNs) 3 play a major role in the development of inflammatory responses to host injury and infection. Their functions include destruction of invading bacteria and recruitment of macrophages and lymphocytes to the affected site (1). Circulating PMNs sense injury and pathogen signals, cross the vascular endothelium, and migrate to the target tissue; two series of events control this process. The first leads to the slowing down and adherence of circulating PMNs on the vascular endothelium followed by their transendothelial migration or extravasation and activation (2). The second controls the directional migration of PMNs to the injured site through the endothelial basement membrane, a specialized type of ECM, and subsequently the deeper interstitial ECM, along chemokine and cytokine gradients. Leukocyte-to-leukocyte and leukocyte-to-endothelium interactions are important before extravasation. These are mediated by interactions between selectins and their ligands and by ␤ 2 (MAC-1 and LFA-1) and ␤ 1 (VLA-4 -6) integrin interactions with cell adhesion proteins ICAM and PECAM (3). The directional migration of PMNs through the ECM is a complex, multistep process that involves several ␣ and ␤ integrin interactions with ECM proteins. Thus far, a few basement membrane proteins, laminins, entactin, and fibronectin have been identified as specific ligands in regulating migration of PMNs after extravasation (4 -6). Additional interstitial ECM proteins and their receptors that modulate PMN migration have yet to be identified. Here we show that the ECM protein lumican is a novel regulator of PMN migration.Lumican is a secreted collagen-binding ECM protein of the corneal, dermal, and tendon stroma, arterial wall, and the intestinal submucosa (7-9). It is a member of the small leucine-rich repeat proteoglycans (10); these were initially investigated in the context of binding collagen and regulating tissue structure and biomechanics (11,12). A body of literature is beginning to indicate that these proteoglycans interact with cytokines, growth factors, and cell surface receptors to modulate cell adhesion, proliferation, and migration (13-16). Lumican and biglycan, another member of this family of proteoglycans, have been recently shown to regulate host response to pathogenassociated molecular patterns (17, 18). Thus, lumican-deficient (Lum Ϫ/Ϫ ) mice are hyporesponsive to bacterial lipopolysaccharide (LPS) endotoxins, and Lum Ϫ/Ϫ macrophages in culture produce lower levels of pro-inflammato...

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“…Beside the aforementioned studies, there is also evidence for the influence of lumican on inflammatory processes. [69][70][71][72][73] Data regarding the role of other 14 members of SLRP family are sparse. Future studies are needed to explore the molecule-specific affinities to different receptors and orchestration of their downstream signaling events.…”

Section: Biglycan Signaling Bridges Innate and Adaptive Immunitymentioning

confidence: 99%

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

2012

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Keratocan and Lumican Regulate Neutrophil Infiltration and Corneal Clarity in Lipopolysaccharide-induced Keratitis by Direct Interaction with CXCL1

Cited by 68 publications

References 25 publications

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Extracellular Matrix Lumican Deposited on the Surface of Neutrophils Promotes Migration by Binding to β2 Integrin

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

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