RUO Cytokines
Chemokines
Multifaceted Regulators of Physiology and Pathophysiology
The immune system is comprised of an arsenal of several cell types, each having distinct and specialized functions, that allow for quick and efficient responses to invasive foreign agents. The invasion of such matter generates an onslaught of inflammatory responses, recruiting several immune cells and proteins, including a special class of small cytokines called chemokines.
Representing the largest class of cytokines, chemokines play an essential role in both physiological and pathological activities by stimulating the migration of certain leukocytes through concentration gradients in a process known as chemotaxis.
Critical to maintaining hemostasis through hematopoietic differentiation and immune surveillance, chemokines also help orchestrate both innate and adaptive immune responses. Chemokine-triggered immune responses often require co-stimulation by primary proinflammatory cytokines, such as IL-1α, IFN-γ and TNF-α. Chemokines possess high levels of specificity; a trait that enables the recruitment of diverse populations of well-defined chemokine subsets and receptors.
Classified into subfamilies by the structural conservation of both cysteine residues and disulfide bonds, chemokine nomenclature reflects several cysteine-grouping motifs and arrangements. Exempting members of a single subfamily, one of two conserved disulfide bonds link the first cysteine residue to the third, while the other links the second cysteine to the fourth. These disulfide bonds contribute to the tertiary and quaternary structures that further define the subfamilies and dictate possible receptor-ligand interactions.
In order to exert biological effect, chemokines will bind with receptors of the G-protein coupled receptor (GPCR) superfamily, which possess seven conserved transmembrane domains with which chemokines can interact. Classified into subfamilies based on the motifs of their ligands, these receptors tend to interact with the chemokines of their eponymous subfamilies. Chemokines and their receptors otherwise tend to interact indiscriminately to stimulate upregulation of adherent chemokines, co-stimulatory cytokines and signaling cascades that polarizes cells to direct chemotaxis.
Chemokine Subfamilies and Nomenclature
C Chemokines - Contain only two conserved cysteine residues linked by a single disulfide bond.
CC Chemokines - Contain four conserved cysteine residues of which the first two, closest to the N-terminal, are adjacent to one another.
CXC Chemokines - Contain four conserved cysteine residues of which the first two, closest to the N-terminal, are separated by a single amino acid.
CX3C Chemokines - Contain four conserved cysteine residues of which the first two, closest to the N-terminal, are separated by three amino acids.
