chemoattractants

Chemoattractants are chemical signals that elicit chemotaxis, the directed migration of cells toward higher concentrations of the signal. They play central roles in innate immunity, development, and tissue repair by guiding leukocytes and other mobile cells to sites of infection, injury, or remodeling. Chemoattractants can be proteins such as chemokines, lipid mediators like leukotriene B4, peptide fragments such as N-formyl peptides from bacteria, and various other small molecules.

Most chemoattractants act by binding to specific cell-surface receptors, many of which are G protein-coupled receptors. Receptor activation triggers intracellular signaling networks, often involving PI3K, Rac, Cdc42, and Rho family GTPases, leading to actin polymerization at the leading edge and cell polarization. The result is persistent, directional movement up the chemical gradient toward higher signal concentration. Cells compare concentrations across their front and rear to bias direction, a process known as gradient sensing. Desensitization and receptor downregulation help prevent overstimulation.

Prominent endogenous chemoattractants include chemokines such as IL-8 (CXCL8), CCL2 (MCP-1), and others; the complement fragment C5a; and lipid mediators such as leukotriene B4. Bacterial products like N-formyl-methionyl-leucyl-phenylalanine (fMLP) also act as potent chemoattractants for neutrophils. While many chemoattractants act to recruit leukocytes, some can act in concurrent roles to modulate activation state or survival at the site.

In pathology, inappropriate or excessive chemotaxis contributes to inflammatory diseases, while controlled chemotaxis is essential for host defense and tissue regeneration.