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Toll‐like receptor‐2 and CD47 co‐stimulatory signaling regulates neutrophil transmigration
Author(s) -
Chin Alex Chung Kyu,
Reaves Titus A.,
Lee Winston Y.,
Peatman Eric J.,
Parkos Charles A.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.320.6
Subject(s) - tlr2 , cd47 , chemotaxis , agonist , receptor , microbiology and biotechnology , chemistry , toll like receptor , innate immune system , proinflammatory cytokine , signal transduction , flow cytometry , inflammation , phagocytosis , immunology , biology , biochemistry
Tissue infiltration by neutrophils (PMN) 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 Toll‐like receptor (TLR) signaling is poorly understood. In this study we assessed the role of TLR2 and CD47 co‐stimulation in regulating PMN transmigration. PMN transepithelial migration (TEM; T84 monolayers) towards the bacterial chemoattractant fMLP was significantly delayed for 30min by 1μM Pam 3 CSK 4 (TLR2/1 agonist), 100nM MALP‐2 (TLR2/6 agonist) or 20μg/ml anti‐human CD47 mAbs (C5/D5). In addition, Pam 3 CSK 4 or MALP‐2 and C5/D5 added together further delayed PMN TEM by 2h. C57BL/6 murine bone marrow‐derived PMN transfilter migration (TFM) towards fNLP was inhibited (50%) by 200nM MALP‐2 or 20μg/ml anti‐mouse CD47 mAbs (MIAP), while, in combination, blocked PMN TFM by 75%. Conversely TFM using TLR2−/− or MyD88−/− bone marrow PMN was not inhibited by MALP‐2 or MIAP. TLR2 agonists did not increase human or murine PMN surface CD47 expression (flow cytometry). Collectively, these findings suggest that TLR activation may serve as “stop” signals, and facilitate antimicrobial functions including CD47‐mediated PMN transmigration.