cathelicidins

Cathelicidins are a family of cationic antimicrobial peptides that form part of the innate immune defense in mammals and other vertebrates. They are produced as inactive prepropeptides and processed to active peptides. In humans, the CAMP gene encodes the cathelicidin precursor hCAP-18, which is cleaved to the mature peptide LL-37. In other species, related peptides with different sequences exist (for example, mouse CRAMP).

Expression and processing: Cathelicidins are synthesized by neutrophils, macrophages, and various epithelial cells, including skin, respiratory, and intestinal epithelia. They are stored as prepropeptides and released and proteolytically processed at sites of infection to yield the active LL-37 or species-specific equivalents.

Functions: They show broad-spectrum antimicrobial activity against bacteria, fungi, and enveloped viruses, largely through disruption of microbial membranes. Beyond direct killing, cathelicidins modulate the immune response: they act as chemoattractants, influence cytokine production, promote wound healing and angiogenesis, and can neutralize bacterial endotoxins such as LPS. They can also enhance adaptive immune responses and show synergistic effects with conventional antibiotics.

Regulation and clinical relevance: CAMP expression is upregulated by vitamin D receptor signaling in keratinocytes and other cells. Dysregulation or deficiency of cathelicidins has been linked to increased infection risk and to inflammatory skin diseases such as atopic dermatitis and psoriasis. Therapeutic applications are investigated, including topical formulations and systemic approaches, but challenges remain regarding stability, delivery, and potential cytotoxicity.

Evolution and diversity: The cathelicidin family is broadly conserved among vertebrates, with species-specific peptides, typically sharing a conserved N-terminal cathelin domain and a rapidly evolving C-terminal antimicrobial domain.