From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
The Membrane Attack Complex (MAC) is a crucial component of the complement system that forms pores in cell membranes to destroy pathogens, representing the final stage of the complement cascade, specifically the terminal pathway, as described in the study by 1.
Overview of MAC
The MAC forms when complement proteins C5b, C6, C7, C8, and multiple C9 molecules assemble sequentially on target cell membranes. This process begins when C5b binds to C6, forming C5b6, which then incorporates C7 to become membrane-associated. C8 then joins this complex, allowing for the polymerization of multiple C9 proteins that create a transmembrane channel or pore.
Function and Regulation
These pores disrupt the cell membrane's integrity, allowing water and ions to flow freely into the cell, causing osmotic swelling and ultimately cell lysis. MAC primarily targets gram-negative bacteria, as gram-positive bacteria have thick peptidoglycan layers that prevent MAC from reaching their cell membranes. Host cells are protected from MAC-mediated damage through regulatory proteins like CD59, which prevents C9 polymerization, as discussed in the study by 2.
Clinical Significance
Dysregulation of MAC formation contributes to various inflammatory and autoimmune conditions, including paroxysmal nocturnal hemoglobinuria and certain forms of glomerulonephritis, where excessive MAC deposition damages host tissues. The use of eculizumab, a humanized antibody that blocks complement activity, has been successfully used in conditions like atypical hemolytic uremic syndrome (aHUS), as reported in the study by 3.
- Key aspects of MAC evolution, function, and structure have been reviewed in the study by 4, providing new insights into the molecular mechanism of MAC assembly.
- The structural basis for eculizumab-mediated inhibition of the complement terminal pathway has been described in the study by 2, explaining how eculizumab functions by sterically preventing C5 from binding to convertases.
- The use of tailored eculizumab therapy in the management of complement factor H-mediated aHUS has been reported in the study by 5, highlighting the importance of prophylactic eculizumab in preventing recurrence after kidney transplantation.