**2.1 Membrane receptors**

Membrane receptors are one of integral membrane proteins. They mediate cell signaling via binding extracellular molecules. Specifically, membrane receptors allow communication between the cell and external environment. Hormones, cytokines, cell adhesion molecules, and immunoproteins are examples of the extracellular molecules. The ligand bound of the membrane receptor may induce changes in the metabolism or activity of the cell. In RC, CD55 (decay-accelerating factor) and


*Membrane receptors consist of CD55 and CD59; transporters consist of AE1, RhAG, nucleoside transporter, urea transporter, and glucose transporter; cell adhesion molecule consists of CD47.*

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**Figure 1.**

*Application of Red Cell Membrane in Nanobiotechnology DOI: http://dx.doi.org/10.5772/intechopen.84274*

is produced by glycolysis of glucose [17].

**2.2 Transporters**

CD59 are well-known membrane receptors which inhibit CS preventing hemolysis (**Figure 1**) [10]. In detail, CS is composed of proximal and terminal complement (**Figure 2**) [4]. The proximal CS has three pathways converged at the step of complement component 3 (C3) activation. The terminal complement is initiated with complement component 5 (C5) and ended with formation of membrane attack complex (MAC). In this cascade, CD55 inhibits C3 activation by deactivating C3 convertase [11]. CD59 inhibits terminal complement activation by preventing the formation of MAC that starts with the activation of C5 [12]. The absence of CD55

Transporters are involved in the movement of specific molecules or ions across cell membrane. The proteins are involved in the movement of molecules by active transport or facilitated diffusion. It is revealed that anion, gas, nucleoside, urea, and glucose transporters are expressed on the RC. In detail, (AE1, also called band 3) is responsible for mediating the exchange of chloride ion with bicarbonate (HCO3ˉ) across RCM [13]. Rh-associated glycoprotein (RhAG) is a gas transporter which permeates carbon dioxide [1]. Nucleoside transporter mediates the transport of nucleoside substrates like adenosine [14]. Urea transporter is specialized in urea transportation, which is activated by antidiuretic hormone (vasopressin) [15]. Glucose transporter (GLUT) is a uniporter that transports glucose toward intracellular orientation (**Figure 3**) [16]. GLUT is an essential protein for glucose uptake of the cell by catalyzing facilitative diffusion. Especially, RC expresses a large number of GLUT compared to other cells because the cell lacks mitochondria and the energy

*Hemolysis mechanism of paroxysmal nocturnal hemoglobinuria (PNH) via the complement system [4]. (a) Normal RBC possesses CD55 and CD59 which are glycosylphosphatidylinositol (GPI)-anchored self-protective complement regulatory factors. CD55 is a widely expressed membrane protein that accelerates the decay of C3 convertases. CD59 is the major inhibitor of terminal complement, which blocks the generation of the membrane attack complex (MAC). (b) Intravascular hemolysis of PNH RBC through C3 convertase and MAC. (c) Extravascular hemolysis of PNH RBC via macrophage. Eculizumab inhibits the complement activation by compensating CD59. \*PNH, a life-threatening disease characterized by destruction of RBC by complement system; eculizumab, a monoclonal antibody complement inhibitor which is highly effective for PNH; C3 con, C3 convertase; C5b-8, complex of C5b, C6, C7, and C8 proteins; C3dg, a fragment of C3 protein, which is ligand of integrin (CR3) on macrophage; iC3b, inactivated C3b; Hb, hemoglobin; CR3, complementary 3.*

and CD59 may lead to hemolysis of RC via complement activation [4].

*a DAF, decay-accelerating factor.*

*b MAC, membrane attack complex.*

*c SIRPα, signal regulatory protein alpha.*

#### **Table 1.**

*Various membrane proteins in RCs [5].*

*Application of Red Cell Membrane in Nanobiotechnology DOI: http://dx.doi.org/10.5772/intechopen.84274*

CD59 are well-known membrane receptors which inhibit CS preventing hemolysis (**Figure 1**) [10]. In detail, CS is composed of proximal and terminal complement (**Figure 2**) [4]. The proximal CS has three pathways converged at the step of complement component 3 (C3) activation. The terminal complement is initiated with complement component 5 (C5) and ended with formation of membrane attack complex (MAC). In this cascade, CD55 inhibits C3 activation by deactivating C3 convertase [11]. CD59 inhibits terminal complement activation by preventing the formation of MAC that starts with the activation of C5 [12]. The absence of CD55 and CD59 may lead to hemolysis of RC via complement activation [4].
