Extra-hepatic transcription of the human mannose-binding lectin gene (mbl2) and the MBL-associated serine protease 1–3 genes

Seyfarth, Jeanette; Garred, Peter; Madsen, Hans O.

doi:10.1016/j.molimm.2005.06.033

Cited by 94 publications

(74 citation statements)

References 43 publications

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“…Lack of MBL2 expression in PBMCs agrees with previous reports, but MBL2 can be induced in vitro in adherent monocyte and monocyte-derived dendritic cells (28). Although expression for some genes (C1Q, C4, and FCN1) was detected in PBMCs as in earlier reports (29-31), MASP2 expression was not detected previously in PBMCs (28). Initiation of the classical pathway is antibodydependent, but the lectin pathway is antibody-independent and begins with the recognition and binding of sugars or N-acetyl groups on pathogenic cells (pathogen-associated molecular patterns) by MBL or FCN.…”

Section: Discussionsupporting

confidence: 92%

“…Gene T0 T1 T2 T0 T1 T2 T0 T1 T2 C1QA - ity is not restricted to specialized cells such as hepatocytes. Lack of MBL2 expression in PBMCs agrees with previous reports, but MBL2 can be induced in vitro in adherent monocyte and monocyte-derived dendritic cells (28). Although expression for some genes (C1Q, C4, and FCN1) was detected in PBMCs as in earlier reports (29-31), MASP2 expression was not detected previously in PBMCs (28).…”

Section: Discussionsupporting

confidence: 91%

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Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Sorensen

Jones

Vernon

et al. 2009

Mol Med

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Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise. We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs. At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (≥2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups. In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 downregulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Sorensen

Jones

Vernon

et al. 2009

Mol Med

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“…Their broad expression may indicate local functions of MASP-3 and MAp44, different from the one they perform in the circulation. The tissue distribution we observed for MASP-1 and MASP-3 mRNA confirms previous reports (35,41).…”

Section: Discussionsupporting

confidence: 92%

MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation

Degn¹,

Hansen²,

Steffensen

et al. 2009

The Journal of Immunology

163

165

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Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 μg/ml in Ca2+-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (KD = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.

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“…The finding that MBL is present in semen is consistent with the work of Seyfarth et al [12], who found that MBL mRNA is transcribed actively in both testis and prostate tissue. In addition, we found this MBL to be capable of binding to bacteria.…”

Section: Discussionsupporting

confidence: 91%

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro

Wing

Jack

Lee

et al. 2009

Clinical and Experimental Immunology

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SummaryMannose-binding lectin (MBL) is an innate immune molecule present in blood and some mucosal tissues, which can influence microbial attachment and inflammatory responses of host cells during infection. In this study MBL was found to be present at a low concentration in semen samples in the range 1·2-24·9 ng/ml. Co-incubation of bacteria with semen resulted in the binding of MBL to the bacterial surface. Neisseria gonorrhoeae is a common cause of genitourinary infection. MBL bound to N. gonorrhoeae with strain-to-strain variation in the intensity of binding and nature of the bacterial receptor. Pretreatment with MBL concentrations similar to those found in human serum modulated the adhesion of N. gonorrhoeae strain FA1090 but not strain MS11 to epithelial cells. This effect was dose-dependent. This work demonstrates that MBL is present in human semen and modifies cellular responses to N. gonorrhoeae in a concentration-dependent manner.

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Extra-hepatic transcription of the human mannose-binding lectin gene (mbl2) and the MBL-associated serine protease 1–3 genes

Cited by 94 publications

References 43 publications

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro

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