Cationic antimicrobial protein of Mr 37 kDa: a multifunctional inflammatory protein

Purpose To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. Data sources Endothelial cells used in this study were obtained from human lung microvessels and rat aorta. The latter was a kind gift of Dr. Paula Gr ammas. The mono-mac 6 cell line used in this study was the generous gift of Dr. H.W. Loms Ziegler-Heitbrock. Study selection and data extraction Endothelial cell proteins kinase C acti vity was determined by measuring calcium- and phospholipid-dependent phosph orylation of histone. Endothelial cell migration was determined using Costa r(TM) Transwell apparatus. Cell surface expression of adhesion molecules, I CAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to a mplify the CAP37 from endothelial cells treated with LPS. Results We demonstrated that CAP37 which was originally identified as havin g potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endotheli al cell protein kinase C in a dose- and time-dependent fashion. Importantly CAP37 increased the adhesive properties of the endothelium for monocytes. CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time- dependent manner. In addition, CAP37 promoted endothelial cell migration. Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory media tors such as lipopolysaccharide. Unstimulated endothelial cells did not con stitutively express CAP37. The cDNA sequence of endothelial CAP37 was deter mined and found to be highly homologous to the sequence obtained for neutro phil-derived CAP37. Conclusions Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues.