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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900789v1 183/9/5957    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Chin, A. C. Articles by Parkos, C. A. PubMed PubMed Citation Articles by Chin, A. C. Articles by Parkos, C. A.

CD47 and TLR-2 Cross-Talk Regulates Neutrophil Transmigration

Alex C. Chin,^12* Bénédicte Fournier,^* Eric J. Peatman,^* Titus A. Reaves, Winston Y. Lee,^* and Charles A. Parkos^2*

^*Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322 and Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC 29425

Neutrophil (PMN) infiltration into tissues is a hallmark of acute inflammation and is crucial for the rapid removal of microbial pathogens. Previous studies have shown that PMN transmigration is regulated by the cell surface protein CD47. However this phenomenon in the context of microbial invasion and subsequent TLR signaling is poorly understood. In this study, we assessed the role of TLR2 and CD47 costimulation in regulating PMN transmigration. Human PMN transmigration across acellular collagen-coated filters toward the bacterial chemoattractant fMLP was more significantly inhibited by MALP-2 (TLR2/6 agonist) than Pam₃CSK₄ (TLR2/1 agonist). Subsequent experiments demonstrated that treatment with MALP-2 or anti-human CD47 mAbs delayed human PMN transfilter migration, while combined treatment led to further delayed inhibition. Interestingly, stimulation of PMNs with MALP-2 resulted in an increase in surface expression of CD11b, but not CD47. In experiments addressing the role of TLR agonists in regulating CD47-mediated PMN transmigration, incubation with MALP-2 or with anti-mouse CD47 mAbs did not inhibit transfilter migration of TLR2^–/– or MyD88^–/–-deficient murine bone marrow-derived PMNs. Similarly, inhibition of MyD88 homodimerization reversed the attenuation of human PMN transmigration induced by MALP-2 or anti-human CD47 mAbs. Separate experiments demonstrated that CD47^–/– murine bone marrow-derived PMNs exhibited 4-fold decreased sensitivity toward MALP-2. Collectively, these findings suggest that activation of CD47 signaling enhances PMN sensitivity toward TLR2 activation which, in turn, signals their arrival at a site of invasion and may facilitate antimicrobial function.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Current address: Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road, Atlanta, GA 30322.

² Address correspondence and reprint requests to Dr. Alex C. Chin, Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road, Atlanta, GA 30322 or Dr. Charles Parkos, Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322. E-mail addresses: achin{at}emory.edu or cparkos{at}emory.edu

³ Abbreviations used in this paper: PMN, neutrophil; PAMP, pathogen-associated molecular pattern.