Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells

Abstract

Most antimicrobial peptides have been discovered based on activity-guided purification procedures, which used assays to determine their antimicrobial activity. Nevertheless, recent studies have shown that antimicrobial peptides also exert a range of other functions. Based on these observations, antimicrobial peptides are now not only implicated in host defense against infection but also in other immune reactions, inflammation, and wound-repair processes. The activities of neutrophil defensins and the cathelicidin hCAP-18/LL-37, antimicrobial peptides that are abundantly expressed in the human neutrophil, are the subject of an increasing number of studies. Exposure to neutrophil defensins and hCAP-18/LL-37 results in increases in mediator expression and release, chemotaxis, and proliferation of inflammatory and epithelial cells and fibroblasts, and the mechanisms underlying these effects have been partly elucidated. This review is focused on the effects of neutrophil defensins and hCAP-18/LL-37 on airway epithelial cells.

Innate immunity of the bovine mammary gland

“…In particular conditions, such as the phagosomes of leukocytes, there is no doubt that host defense peptides contribute to the killing of ingested bacteria, but in extracellular situations, immunomodulatory properties are likely to be of more significance [18]. A number of human antimicrobial peptides have been shown to possess chemotactic activity for monocytes, immature dendritic cells and T-lymphocytes, and they can also induce the secretion of IL-8 by epithelial cells, and proliferation of epithelial cells and fibroblasts [48,195]. Model peptides devoid of direct antimicrobial activity were found to be protective in animal models of S. aureus and Salmonella infections, implying that host defense peptides can protect through immunomodulatory properties [19].…”

Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome

“…They have chemotactic activity for neutrophils, eosinophils, monocytes, dendritic cells and T-cells. Additionally, they affect maturation and upregulate the endocytic capacity and co-stimulatory molecule expression of dendritic cells, and promote the repair of epithelial surfaces by cell proliferation and inhibition of apoptosis [17][18][19][20][21]. AMPs play a key role in orchestration of the subsequent adaptive cellular or humoral response to injury favouring a repair response.…”

Mechanistic and Functional Studies of the Interaction of a Proline-rich Antimicrobial Peptide with Mammalian Cells

“…These molecules all exhibit a net positive charge at neutral pH and an overall amphipathic topology that favors their binding to and insertion into anionic phospholipids, leading to rapid disruption of the bacterial membranes (2,3). AMPs efficiently kill a variety of microbial pathogens both in vitro and in vivo (2,4), and some of them have been shown to also modulate various cellular responses (5,6). The latter finding has led to a re-evaluation of the role of AMPs in immunity, suggesting their involvement in recruitment, activation, and/or maturation of inflammatory and immune cells and/or tissue repair (5,6).…”

“…AMPs efficiently kill a variety of microbial pathogens both in vitro and in vivo (2,4), and some of them have been shown to also modulate various cellular responses (5,6). The latter finding has led to a re-evaluation of the role of AMPs in immunity, suggesting their involvement in recruitment, activation, and/or maturation of inflammatory and immune cells and/or tissue repair (5,6). The multiple activities of AMPs underscore their capacity to interact with host cells by binding to cell surface receptor(s), as exemplified by binding of the ␣-helical peptide LL-37 to the formyl peptide receptor-like 1 (7), or by binding intracellular targets, as indicated by the ability of the proline-rich cathelicidin peptide PR-39 to interact with various cytoplasmic proteins (8 -10).…”