NEUTROPHILS: SOPHISTICATED & ADAPTABLE DEFENSE MACHINES
Neutrophils are a major subset of white blood cells (leukocytes), which protect the body against pathogenic microorganisms and other dangers. The historical view of neutrophils as unsophisticated, terminally-programmed killers has recently been overturned by new experimental evidence underscoring their strong abilities for reprogramming and functional adaptation. Evolving concepts in neutrophil biology open exciting opportunities for neutrophil-targeted therapies for many important diseases. Celtaxsys is at the forefront of translating the new science of neutrophils into innovative treatments for inflammatory diseases.
Introduction to Neutrophils
Neutrophils are immune cells that are easily recognized by their characteristic multi-lobed cell nucleus. They are part of the innate immune system with the ability to recognize and neutralize a wide variety of biological and environmental threats. In humans, neutrophils are the most abundant white cells in blood, accounting for about 60-70%. Neutrophils are generally shorter-lived than other white blood cells, and it is estimated that about 10 billion new neutrophils are produced every day. When a potential threat is sensed, such as an invading microorganism, neutrophils are among the first immune cells to respond. However, disease states can be initiated or promoted as a consequence of neutrophil activity against invasive organisms or by misdirected neutrophil attack on host tissues. Despite their prevalence and connection with many inflammatory diseases, there has been minimal progress toward discovery of neutrophil-directed treatments. In part, this effort is hampered by the difficulty of working with neutrophils, which are very short lived and not readily propagated outside the body. Celtaxsys harvests fresh neutrophils several times per week to ensure its research is conducted using only the highest quality and most realistic cells.
Neutrophils Express a Wide Variety of Functions and States
Historical models describe neutrophil function as a one-way trip from bone marrow, through blood, and into tissues, where they hunt and eliminate their targets before being eliminated themselves after dying and being scavenged by other immune cells called macrophages. However, this view of neutrophils as unsophisticated cells exclusively involved in acute responses has been decisively challenged in the past decade.
We now know that to help them fulfill their defensive duties, neutrophils have evolved a variety special features that include:
- An unmatched diversity of surface receptors, including adaptive receptors, that sense all kinds of danger signals;
- A highly condensed, squeezable cell nucleus and highly deformable cellular skeleton that enable swift movement out of the bloodstream and through blood vessel walls and tissues in active pursuit of their targets (a process known as chemotaxis);
- A highly developed ability to engulf (phagocytose) targeted microorganisms or solid particles and encase them within cellular digestive vesicles, a kind of cell stomach;
- An array of cellular storage compartments (granules) containing specialized receptors, enzymes and bioactive molecules that can be shuttled to cellular digestive vesicles or released outside the cell in order to kill and eliminate invading microorganisms;
- The ability to change their phenotype and even extend their lifespan based on local conditions in order to promote or resolve inflammation; and
- The ability to orchestrate the actions of other cells, most notably cells of the adaptive immune system such as B-cells and T-cells.
Together, these characteristics make the neutrophil a fast-moving, smart, and deadly weapon against invading microorganisms. When gone awry, however, these same features can make the neutrophil a primary mediator of pathological inflammation.
Functional modulation of neutrophils
Neutrophils have been recognized as sophisticated, multifaceted cells with 4 main functions: 1- patrolling in blood; 2- two-way migration to and from tissues; 3- multimodal killing; and 4- chronic adaptation processes. Current treatments are not adequate for modulating these 4 main functions, emphasizing the need for novel, “smart” drugs targeting neutrophil-related diseases.
Further Reading
How neutrophils kill microbes. Segal, AE. Annual Reviews in Immunology (2005) 23:197-223. Review. PMID: 15771570
Neutrophils in the activation and regulation of innate and adaptive immunity. Mantovani, et al. Nature Reviews Immunology (August 2011) 11, 519-531. Review.
