Phagocytosis and pinocytosis are the primary types of endocytosis, a cellular process in which cells absorb extracellular material by invagination of the cell membranes. Both are the active process and requires energy (ATP) as adenosine triphosphate for the uptake of materials. Endocytosis uses to transfer material from outside the cell to intracellular spaces.
In mammalian cells, it is regulated by the alternation in the function and composition of the plasma membrane. Endocytosis basically regulates diverse processes in the cell such as homeostasis of the cell, signal transduction, entry of pathogens (bacteria and viruses).
Phagocytosis first observed by the Elie Metchnikoff. The word phagocytosis is derived from the Greek word φαγεῖν (phagein) means to eat. It is a specific type of endocytosis by which cell intake solid particles by the deformation in the plasma membrane resulting in the formation of the vesicles called a phagosome.
The engulf particles are digested in the phagosome by the enzyme. These enzymes are present in the lysosomes which combine with the phagosome. The ingested particles are broken down into simpler particles before the absorption.
The solid particles include cell debris, foreign antigen, microorganism, etc. It is the ingestion of large particles around 1-2μm in size. It is mediated by recognition and binding with extracellular particles or pathogens via specific cell surface receptors. These receptors lead to the membrane deformation, Pseudopod extension subsequent contraction to engulf particles.
Cells involved in the phagocytosis are called phagocytic cells. The phagocytic process is of great importance. It is used in the defense purpose one of the main parts of the innate immunity and play a role in the first line of defense against the infection or foreign particle and also a major role in the adaptive immune response. Different types of cells especially immune cells are involved in the phagocytosis of solid particles including neutrophils, eosinophils, monocytes, macrophages, dendritic cells, and B-lymphocytes.
They are phagocytic cells present in blood stream and circulate in the blood and spleen. They make up about 5% to 10% of white blood cells. Monocytes that migrate into tissues in response to infection can differentiate into specific tissue macrophages.
They phagocytose dead cells and foreign bodies including pathogen in response to production of nitric oxide. Macrophage are of two types either fixed macrophage or wandering macrophage. Activated macrophages are more effective than resting ones in eliminating potential pathogens by phagocytosis.
They are motile phagocytic cells but their role as phagocytic cells is less significant than neutrophils and macrophages. Their main role is against the multicellular parasitic organisms, including worms that are not easily phagocytosed. They form clusters around invading worms, whose membranes are damaged by the activity of proteins released from eosinophilic granules.
They are the most abundant WBCs, constitute the majority (50% to 70%) of circulating leukocytes. They phagocytic in nature, motile phagocytic cells, and Metchnikoff called them the archetypal phagocyte. They phagocytose and killed the pathogen by using reactive oxygen species.
Dendritic cells (DCs)
They are professional phagocytes and phagocytose parasites, bacteria, cell debris, or even intact cells very efficiently.
Steps of Phagocytosis
There are following steps invoved in the phagocytosis:
- Activation of the Phagocyte
- Chemotaxis of Phagocytes
- Attachment of the Phagocyte to the extracellular particle (microbes or cell)
- Ingestion of the microbes or cell by the Phagocyte
- Destruction of the microbes or cell
1: Activation of the Phagocyte
Phagocytic cells are activated by the inflammatory mediators that are either a whole-cell e.g. bacteria or virus or any component of the cell such as bacterial proteins, capsules, peptidoglycan, prostaglandins, complement proteins. After the activation of the phagocytic cell rearrangement of the cytoskeleton of the cell is occurred and the phagocytic cell enters into the tissue from the capillaries to reach the infection site.
They produce pattern recognition receptors (PRRs) that are involved in the recognition of the pathogen and bind with the pathogen-associated molecular patterns (PAMPs) which are present on the surface of the pathogen. These PAMPs are the component of the pathogen and include peptidoglycan and lipopolysaccharide (LPS).
2: Chemotaxis of Phagocytes
Chemotaxis is a reaction by which the direction of movement of the cells is determined in response to the stimuli by the chemical substance. This directs the phagocytic cells to the site of infection or the area where high concentration of foreign particles, cells or molecules are present and thus promote the phagocytosis process.
Different types of chemotactic molecules called attractants are bacterial products, cell and tissue debris, and components of the inflammatory exudate such as peptides derived from complement.
3: Attachment of the Phagocyte to the extracellular particle (microbes or cell):
This step involves receptors present on the phagocytic cell membrane and necessary for the for the molecule to be ingested. Receptors present on the phagocytic cells bind with the particles or pathogen through PAMPs or other receptors and initiate the phagocytosis. The phagocytic cells such as macrophages will not initiate the phagocytosis if the surface receptors are not successfully bind.
There are different receptors used for phagocytosis that depend on the phagocytic cells. But the following receptors are mostly used for binding
Opsonins make bacteria or viruses to more easily ingestible by the phagocytes as it provides extrinsic ligands for phagocytic receptors which enhance attachment of the particles with the phagocytic receptor subsequently increase ingestion of the pathogen. These receptors have ability to bind with the bacteria or other immunoglobulin G antibodies coated particles.
These receptors recognize and bind to a variety of lipid-related ligands molecules that are produced by the bacteria, modified and unmodified host-derived molecules. They also bind the ligands which are derived from the host cell that are damaged, apoptotic, or senescent These receptors used to phagocyte the unopsonized target.
These receptors bind to the bacterial molecules and and promote phagocytosis. TLR-induced phagocytosis of bacteria presents on the myeloid differentiation 88 factor and lead the up-regulation of scavenger receptors. There are lots of different types of Toll-like receptors produced by the body, all which bind different molecules. TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process.
Antibodies enhance the process of phagocytosis. Antibodies are basically proteins that bind to the microorganism and promote the engulfing by the phagocytosis.
4: Ingestion of the microbes or cell by the Phagocyte
The membrane start surrounding the molecule by physical or chemical changes in the cell that triggers ingestion. The phagocytic cell surrounds the molecule by infolding the plasma membrane resulting in the formation of the vacuole called the phagosome.
The ingestion of the molecule depends upon the size of the molecule as the small molecules such as bacteria etc. are ingested more instantaneously while the large molecules such as cluster of bacteria or clumps of tissues are phagocytosed more over the time.
5: Destruction of the microbes or cell
Hydrolytic enzyme (phagocytic enzymes) digest the ingested molecules. Bacteria are killed followed by the lysis and digestion by the lysosomal enzymes that are present within the membrane.
Pinocytosis word derived from Greek word pinos mean to drinking. It was discovered by the Warren. H lewis in 1931. It is the process of ingestion of the small particles (liquid particles) that are suspended in the extracellular space through small vesicles.
These vesicles are formed due to the invagination of the plasma membrane and pinosomes. As it includes transport of large tiny particles through the fluid it is also known as fluid endocytosis or bulk-phase endocytosis.
It is constitutive process that occur continuously. It is not substrate specific and used for intake of material or surrounding material that are required for the survival of the cell such as sugars, ions, amino acids, enzymes, hormones etc. Unlike the phagocytosis, there is no role of lysosome in the pinocytosis and also exocytosis not occur at the end of the pinocytosis process.
Pinocytosis usually occur in almost all cells of the body particularly occurs in secreting cells and cell lining of the blood capillaries.
Types of Pinocytosis (based on the molecular size of particles)
Based on the size of the molecule that is intake during pinocytosis, there is two main types of pinocytosis.
In this type of pinocytosis small vesicles are formed as small molecules intake by it. The size of vesicles formed are of about 0.1μm in length. Small depressions are formed on the cell surface after the entry of the molecules. It plays important role in transfer of molecule across capillaries walls. Example of micropinocytosis is Caveolin-mediated pinocytosis.
It is the process of intake large molecules into the cells from outside the cell. Large invagination are formed due to intake of large molecule resulting in rather large vacuole formation of size about 1-2μm. The pockets formed in the plasm membrane during macropinocytosis are the result of rearrangement of actin filaments of cytoskeleton. Example include uptake of nutrients by the amoeba. It is also used in motility for migrating cells as it helps in the coordination insertion and uptake of plasma membrane with their direction of motion.
Types based on receptors
There are following types of pinocytosis based on receptors involved in it.
- Clathrin-mediated pinocytosis
- Caveolin-mediated pinocytosis
- Clathrin- and caveolin- independent pinocytosis
Basic Steps of Pinocytosis
Extracellular fluid present containing the desired material initiate the pinocytosis process which is inducer substances
- The inducer substance binds to the receptor on the plasma molecules and it invaginates.
- As the plasma membrane invaginates it forms a pocket or cavity that fills with the extracellular fluid and dissolved molecules.
- The plasma membrane folds back on itself and starts to reconnect the open end of the plasma membrane.
- This pinched off of the membrane formed the vesical and cut off the vesicle from the membrane
The vesicle moves into the cytoplasm. The molecules inside the vesicle release out to use by the cell
Examples of Pinocytosis
- Kidney cells use pinocytosis which helps them to separate the nutrients and fluid from the urine.
- Pinocytosis also occurs in the microvilli in the small intestine to absorb nutrients from the food.
- Human eggs also used it to absorb nutrients.