MadSci Network: Cell Biology
Query:

Re: Agents that stimulate pinocytosis

Date: Tue Oct 30 17:54:56 2007
Posted By: Cenk Sumen, Post-doc/Fellow, Immunology, Memorial Sloan-Kettering Cancer Center
Area of science: Cell Biology
ID: 1193087971.Cb
Message:


Pinocytosis involves the fluid-phase takeup of extracellular media by cells undergoing membrane 
invagination. As such, it is a form of endocytosis. I will limit the next two paragraphs to 
mammalian cells, although it is likely that all eukaryotic cells can undergo some form of 
pinocytosis. Known examples of this process in non-mammalian cells include the parasitic 
protozoan Entamoeba histolytica (causes amoebic dysentery) and Dictyostelium, a slime mold 
studied often in cell biology to determine cellular components affecting locomotion. 
Requirements for pinocytosis in these unicellular organisms, including plasma membrane 
cholesterol and lipid rafts, mirror that of mammalian cells. Membrane flexibility and integrity 
seem to be universal requirements for unicellular and multicellular life.

Neutrophils and macrophages are the two cell types that have been most commonly used to 
study pinocytosis. These phagocytic cells are the vanguard of the immune response, and often 
rush into inflamed sites to engulf microorganisms, damaged cells and other debris. Although 
these latter functions featuring the specific takeup of particles are more likely to involve directed, 
receptor dependent endocytosis, pinocytosis can also play an important role. Pinocytosis can aid 
the clearance of bacterial toxins, or the dampening of the immune response by the clearance of 
soluble activating factors. Apart from the absorption of the trapped volume of liquid that is 
internalized with each pinocytosed vesicle, the process also allows the recycling of membrane 
components that would otherwise build up during degranulation as secretory vesicles are 
delivered to the membrane to release their cargo to the outside environment. 

The surprising thing about pinocytosis is that unactivated macrophages have a very low amount 
of background pinocytosis. Hence, the primary event that stimulates pinocytosis is the activation 
of the cell. This can occur through numerous molecular pathways, such as kinase networks, and 
involve release of intracellular ions such as Ca2+. There is a long list of substances that can 
activate macrophages, such as bacterial lipopolysaccharides, CpG motifs in DNA, low density 
lipoproteins, and antibodies via Fc receptors. Hence all of these diverse substances can activate 
pinocytosis. It's like keeping track of daily stimuli that can arouse anger in a person, and trying 
to find a commonality. It would be very difficult to catalogue an extensive list and such a 
collection would always be context dependent. Nonetheless, we can be fairly certain that once 
angry, people will undergo predictable changes in behavior and physiology. 

As far as positively charged ions, it has been known for some time that small peptides containing 
positively charged amino acids (such as Lys and Arg) can be taken up non-specifically by 
mammalian cells, through an unknown mechanism that likely shares features with pinocytosis. 
However, the cells still need to be activated by other means. These peptides likely bind to the 
phosphate head groups of lipids on the outer leaflet of the plasma membrane, which are 
negatively charged. One must be careful to discriminate between agents that cause a process 
from ones that merely participate in it. 




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