CAP37, a Novel Inflammatory Mediator

Abstract

Cationic antimicrobial protein of 37 kd (CAP37), originally isolated from human neutrophils, is an important multifunctional inflammatory mediator. Here we describe its localization within the vascular endothelium associated with atherosclerotic plaques. Evidence from in vitro immunocytochemical, Northern blot, and reverse transcriptase-polymerase chain reaction analysis indicates that CAP37 is induced in endothelial cells in response to inflammatory mediators. Endothelial-derived CAP37 shows sequence identity with an extensive region of neutrophil-derived CAP37. This is the first demonstration of endogenous endothelial CAP37, confirmed by sequence analysis. We suggest that, because of its induction and location in the endothelium and its known monocyte- and endothelial-activating capabilities, CAP37 has potential to modulate monocyte/endothelial dynamics at the vessel wall in inflammation.

The Multifaceted Functions of Neutrophils

“…MPO-generated ROS that promote endothelial cell apoptosis, tissue factor expression, low-density lipoprotein nitration, and lipid peroxidation may advance lesion development (193). Many neutrophil granule proteins, including azurocidin, LL-37, and α-defensins, are also found in human atherosclerotic lesions, suggesting that activated neutrophils may directly contribute to lesion development (194, 195). Studies in mouse models of atherosclerosis and indirect evidence in human samples suggest that many of these neutrophil-derived factors attract monocytes and influence their activation status (196).…”

Novel Therapies Based on Cationic Antimicrobial Peptides

“…We found that CAP37 was expressed in endothelial cells [71] and smooth muscle cells [63] associated with the plaque but that it was not present in normal areas of the vessel wall. Not only did these studies demonstrate the association of CAP37 an antimicrobial protein of the innate immune system with atherosclerosis but it also demonstrated the presence of an induced form of CAP37.…”

“…We investigated the biological significance of CAP37 in atherosclerosis by exploring its localization in atherosclerotic lesions [71]. We found that CAP37 was expressed in endothelial cells [71] and smooth muscle cells [63] associated with the plaque but that it was not present in normal areas of the vessel wall.…”

“…Not only did these studies demonstrate the association of CAP37 an antimicrobial protein of the innate immune system with atherosclerosis but it also demonstrated the presence of an induced form of CAP37. Corroborative in vitro studies showed that CAP37 expression could be induced in endothelial cells in response to cytokines such as tumor necrosis factor-α (TNF-α) and injurious mediators such as lipopolysaccharide (LPS) [71] and in smooth muscle cells in response to platelet-derived growth factor (PDGF) [63].…”

The Complexity of Arterial Classical Monocyte Recruitment

“…Once adhering to the vessel wall, neutrophils release soluble components such as azurocidin, which is cationic in nature and therefore favors immobilization on the endothelium, where it is presented to rolling monocytes and promotes their firm adhesion [73]. This is complemented by the capacity of azurocidin to increase expression of adhesion molecules [74,75]. Other neutrophil-borne antimicrobial peptides described to possess monocyte-attracting activity are cathepsin G [76], cathelicidins (LL37 in humans, CRAMP in mice) and defensins [77], all of which can be found in plaques [15,78].…”