Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

Takahashi, Kazue; Chang, Wei‐Chuan; Takahashi, Minoru; Pavlov, Vasile I.; Ishida, Yumi; Bonte, Laura La; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Cott, Elizabeth M. Van

doi:10.1016/j.imbio.2010.02.005

Cited by 86 publications

(95 citation statements)

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“…36 Also, the activation of MASPs can induce the formation of fibrin clots, 25 and human MBL-MASPs complex can mimic thrombin and initiate coagulation. 33 The procoagulant effects of lectin pathway proteins may contribute to eliminating invading pathogens by sequestering them though local activation of the coagulation cascade preventing dissemination throughout the organism. 36 However, local prothrombotic events in injured brain vasculature may impair reperfusion and enhance brain damage after acute ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Because the lectin pathway can induce thrombin activation, 24,33 we examined whether thrombin was involved in the detrimental effects of MBL by treating the mice with the direct thrombin inhibitor argatroban and measuring infarct volume at 24 hours ( Figure 5A and 5B). After MCAO, the reduction in cortical perfusion (mean±SD) as assessed by laser Doppler was 79±10% in the vehicle/WT group, 85±6% in the argatroban/ WT group, 87±6% in the vehicle/MBL KO group, and 81±8% in the argatroban/MBL KO group (P=0.15).…”

Section: Argatroban Reduced Infarct Volume and Ameliorated Neurologicmentioning

confidence: 99%

Section: Argatroban Reduced Infarct Volume and Ameliorated Neurologicmentioning

confidence: 99%

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Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

Rosa

Cervera

Kristoffersen

et al. 2014

Stroke

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Background and Purpose-Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/ reperfusion and influences the course and prognosis of ischemic stroke. Methods-Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation. Results-Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice. Conclusions-MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion. (Stroke. 2014;45:1453-1459.)Key Words: brain ◼ complement pathway, mannose-binding lectin ◼ complement system proteins ◼ infarction, middle cerebral artery ◼ reperfusion Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in MiceXavier de la Rosa, MS; Alvaro Cervera, MD, PhD; Anna K. Kristoffersen, PhD; Claudia P. Valdés, MS; Hari M. Varma, MS; Carles Justicia, PhD; Turgut Durduran, PhD;Ángel Chamorro, MD, PhD; Anna M. Planas, PhD Received November 11, 2013; final revision received February 26, 2014; accepted February 28, 2014. MethodsAn extended version of methods can be found in the online-only Data Supplement. Animal WorkAnimal work was undertaken with approval of the Ethical Committee of the University of Barcelona and in compliance with the Spanish law. Adult (3-4-month-old), male wild-type (WT) and MBL KO mice 31 in the C57BL/6J background were used. 17 Brain Ischemia/ReperfusionIschemia was produced by intraluminal 90-minute occlusion of the right middle cerebral artery (MCAO) in WT (n=83) and MBL KO (n=85) mice. Cerebral perfusion was assessed with laser Doppler flowmetry (Perimed AB, Järfälla, Sweden). A neurological score ranging from 0 (no deficit) to 20 (maximal deficit) was performed at days 1 and 7 after MCAO. MRI StudiesMRI was performed in a 7.0-T ...

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Section: Discussionmentioning

confidence: 99%

Section: Argatroban Reduced Infarct Volume and Ameliorated Neurologicmentioning

confidence: 99%

See 1 more Smart Citation

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

Rosa

Cervera

Kristoffersen

et al. 2014

Stroke

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“…Although often viewed as distinct, they are highly integrated, with several recently identified cross-talk pathways. [22][23][24][25][26][27][28][29][30] For example, thrombin activates C5 and enhances formation of the MAC. 31 Conversely, C5a promotes expression of tissue factor and plays a role in the antiphospholipid antibody-associated fetal loss syndome.…”

Section: Introductionmentioning

confidence: 99%

“…32 Several other biochemical connections have been documented. 29,33,34 In spite of evidence of links between coagulation and complement, the possibility that polyP regulates complement in mammalian systems is unexplored. In a mutant Neisseria meningitidis, lack of the polyphosphatase that normally degrades polyP renders the bacteria resistant to complement-mediated death, indicating that polyP facilitates evasion from complement-mediated killing.…”

Section: Introductionmentioning

confidence: 99%

Polyphosphate suppresses complement via the terminal pathway

Wat¹,

Foley²,

Krisinger³

et al. 2014

Blood

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Collectins

Thiel¹,

Takahashi²

2013

Encyclopedia of Life Sciences

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Collectins are pattern‐recognition molecules of innate immunity and are involved in recognising pathogens and abnormal cells in an antibody‐independent manner. The name collectin is derived from the basic structure, consisting of a collagen‐like domain and a carbohydrate‐recognition domain (CRD), akin to lectins, which recognise sugars. The CRDs bind pathogen‐associated molecular patterns, which are chemical motifs exposed on the surface of pathogens and abnormal cells. Collectins are synthesised in many organs and some are circulating in blood, whereas others are localised to a tissue. Collectin genes are germinally present and therefore, their proteins are expressed at healthy state, affording an instant action. There are also a homologous protein family called ficolins, which are similar to collectins structurally and functionally. Mechanisms of actions include a direct opsonin activity, activation of complement pathways and coagulation, modulation of inflammation and adaptive immunity. Key Concepts: Collectins are molecules of innate immunity, which is the first line of host defence and is fully functional throughout the body and the life regardless of health. Collectins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues. Selected genetic mutations affect functions of collectins and are associated with reduced host defence mechanisms and developmental disorder. Some collectins are disease modifier, as deficiency itself may cause no problem whereas it may have adverse effect depending on type of disease, infection or sterile injury. Collectins have homology to ficolins structurally and functionally, and may share and substitute functions in host defence.

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Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

Cited by 86 publications

References 61 publications

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

Polyphosphate suppresses complement via the terminal pathway

Collectins

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