Makropinoosi

Makropinoosi, or macropinocytosis, is a form of endocytosis in which a cell internalizes extracellular fluid and soluble molecules through large vesicles called macropinosomes. It is energy-dependent and occurs in many cell types, most prominently in macrophages, dendritic cells, and some cancer cells. Unlike receptor-mediated uptake, macropinocytosis is largely non-specific and does not require clathrin or caveolin.

The process begins with actin-driven membrane ruffling at the cell surface, forming large, cup-like protrusions that fold back to enclose extracellular fluid. Closure of these ruffles yields macropinosomes typically ranging from about 0.2 to 5 micrometers in diameter. Macropinosomes often fuse with endosomes and lysosomes for processing of contents.

Regulation involves signaling pathways that activate actin remodeling, including Rac1 and other Rho-family GTPases and phosphoinositide 3-kinase (PI3K). Receptor signaling and growth factors can enhance macropinocytosis, whereas inhibitors such as amiloride or its derivatives reduce it by blocking Na+/H+ exchange.

Physiological and pathological roles include antigen uptake and presentation by dendritic cells and macrophages, immune surveillance, and the exploitation of macropinocytosis by some pathogens for entry. In cancer, Ras-driven tumors can upregulate macropinocytosis to scavenge extracellular proteins as nutrient sources under stress.

Macropinocytosis is distinct from phagocytosis and clathrin-mediated endocytosis in its size scale, non-specific cargo uptake, and lack of vesicle-coating requirements. It remains an active area of study for understanding immune function and cancer metabolism.