title: Haemoglobin scavenging after subarachnoid haemorrhage.
abstract: Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK, andrew.durnford@uhs.nhs.uk.
authors.forename: A
authors.initials: A
authors.lastname: Durnford
authors.forename: J
authors.initials: J
authors.lastname: Dunbar
authors.forename: J
authors.initials: J
authors.lastname: Galea
authors.forename: D
authors.initials: D
authors.lastname: Bulters
authors.forename: J A R
authors.initials: JA
authors.lastname: Nicoll
authors.forename: D
authors.initials: D
authors.lastname: Boche
authors.forename: I
authors.initials: I
authors.lastname: Galea
mesh_terms: D015703:Antigens, CD / Q000134:cerebrospinal fluid*; D015214:Antigens, Differentiation, Myelomonocytic / Q000134:cerebrospinal fluid*; D006242:Haptoglobins / Q000134:cerebrospinal fluid*; D006454:Hemoglobins / Q000134:cerebrospinal fluid*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011956:Receptors, Cell Surface; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications; D014015:Tissue Banks; D015854:Up-Regulation; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000517:prevention & control; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface