Mannose binding lectin and complement pathway in brain ischemic injury: studies in mouse models and patients
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چکیده
pag. 4 INTRODUCTION: pag. 6 Section 1: Stroke Epidemiology 7 Risk Factors 8 Major recognized mechanisms for ischemic stroke 8 Pathophysiology of ischemic stroke and SAH 8 Section 2: Immune mechanism of stroke pag. 13 The complement system in stroke 18 The lectin pathway 22 Section 3: MBL in health and disease pag. 24 General features of MBL 24 Human MBL: from gene to protein 25 The organization of the human MBL2 gene 25 The structure of the human MBL protein 28 Genetic variations in the MBL2 gene 28 The MBL2 genetic polymorphism 29 Maintenance of high frequencies of MBL2 variant alleles in different populations 32 II Consequences of MBL2 gene variations on MBL serum levels 33 Clinical impact of various MBL levels 34 Low MBL levels: role in infectious and autoimmune diseases 34 Low MBL levels: role in ischemic injury 34 MBL therapy: inhibition and replacement 36 MBL related proteins 37 MBL associated serine proteases (MASPs) 37 Section 4: Ficolins in health and disease pag. 38 General features of ficolins 38 Clinical impact of ficolins in ischemic injury 40 AIM OF THE STUDY pag. 42 MATERIALS AND METODS pag. 47 Section 1: Brain ischemia in mice 48 Animals 48 Experimental focal ischemia 48 Transient ischemia 49 Permanent ischemia 50 Sham surgery 51 Intracardiac perfusion 51 Neurological deficits 52 Quantification of infarct size and edema 52 Immunofluorescence and confocal analysis 53 Elisa of functional MBL/MASP-2 54 Western blot of C3 fragments 54
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One of the important parts of innate immunity is complement system that occurs in three different ways; the classic, the alternative and the lectin pathway. The four pattern recognition molecules that have been identified till now are Mannose binding lectin (MBL), a component of lectin pathway, and three ficolins (ficolin1,-2 and -3) which compound to the carbohydrates of the cell surface. MBL ...
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