Regulator Of Membrane Attack Complex Research Articles

Recruitment of Vitronectin by Bacterial Pathogens: A Comprehensive Overview.

The key factor that enables pathogenic bacteria to establish successful infections lies largely in their ability to escape the host's immune response and adhere to host surfaces. Vitronectin (Vn) is a multidomain glycoprotein ubiquitously present in blood and the extracellular matrix of several tissues, where it plays important roles as a regulator of membrane attack complex (MAC) formation and as a mediator of cell adhesion. Vn has emerged as an intriguing target for several microorganisms. Vn binding by bacterial receptors confers protection from lysis resulting from MAC deposition. Furthermore, through its Arg-Gly-Asp (RGD) motif, Vn can bind several host cell integrins. Therefore, Vn recruited to the bacterial cell functions as a molecular bridge between bacteria and host surfaces, where it triggers several host signaling events that could promote bacterial internalization. Each bacterium uses different receptors that recognize specific Vn domains. In this review, we update the current knowledge of Vn receptors of major bacterial pathogens, emphasizing the role they may play in the host upon Vn binding. Focusing on the structural properties of bacterial proteins, we provide details on the residues involved in their interaction with Vn. Furthermore, we discuss the possible involvement of Vn adsorption on biomaterials in promoting bacterial adhesion on abiotic surfaces and infection.

Intravitreal Injection of Amyloid β1-42 Activates the Complement System and Induces Retinal Inflammatory Responses and Malfunction in Mouse.

To investigate whether intravitreal injection of amyloid β1-42 (Aβ1-42) activates the complement system and induces retinal inflammatory responses and malfunction, Aβ1-42 was applied intravitreally in mice. The expressions of key components of complement system were determined by real-time PCR. Retinal function was assessed by electroretinography. We found interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in Aβ1-42 treated mice retinas increased from day 1 to day 7. Compared with control group, mRNA expression of C1qa and C3 in the Aβ1-42 treated retinas increased at days 1 and 7. The level of CFB, CFD, or CFH increased at day 4 and day 7. Regulator of membrane attack complex (MAC), CD59a, increased from day 1 to day 7. The expression of the main complement components in Aβ1-42 treated eyes increased at days 4 and 7. Therefore, our results suggested that exogenous Aβ1-42 activated CP and AP of the complement system in mice retinas, induced retinal inflammatory responses, and caused retinal malfunction.

CD59a deficient mice display reduced B cell activity and antibody production in response to T-dependent antigens

CD59a is the primary regulator of membrane attack complex in mice. Recently, we have shown that CD59a-deficient (Cd59a −/−) mice exhibit enhanced CD4 + T cell responses. Here, we explored the effects of CD59a on B cell function and antibody production. Contrary to our expectations, Cd59a −/− mice showed a decreased humoral immune response to a T cell dependent antigen, sheep red blood cells. We found that the decreased humoral immune response was associated with a reduction in plasma cell number in vivo and reduced ability to respond to stimuli during in vitro culture experiments. Using MLR studies in which purified wild type or Cd59a −/− CD4 + T cells were mixed with purified B cells from each source, we found that the reduced B cell activation was largely due to the absence of CD59a on CD4 + T cells. Furthermore, a CD59a fusion protein bound specifically to mouse B cells, and enhanced B cell proliferation in a MLR, demonstrating that B cells express an as yet unidentified ligand for CD59a that aids in B cell activation.