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Published on: May 22, 2014
Cationic antimicrobial protein of Mr 37 kDa: a multifunctional inflammatory protein
1Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma 73190, USA. Anne-Pereira@ouhsc.edu
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 Grammas. 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 activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone. Endothelial cell migration was determined using Costar Transwell apparatus. Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS.
Results:
We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endothelial 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 mediators such as lipopolysaccharide. Unstimulated endothelial cells did not constitutively express CAP37. The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-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.
Insights
Cationic antimicrobial protein (CAP37) from neutrophils modulates endothelial cell function, increasing monocyte adhesion and migration. CAP37 is induced by inflammatory signals, highlighting its role in monocyte-endothelial interactions.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Neutrophils release cationic antimicrobial protein of Mr 37 kDa (CAP37), an inflammatory mediator.
- The function of CAP37 in endothelial cell biology is not fully understood.
Purpose of the Study:
- To investigate the role of CAP37 in endothelial cell function.
- To determine CAP37's effect on monocyte-endothelial cell interactions.
Main Methods:
- Endothelial cells from human lung microvessels and rat aorta were used.
- Protein kinase C activity, cell migration, and adhesion molecule expression (ICAM-1, PECAM-1) were measured.
- RT-PCR was employed to detect CAP37 expression in endothelial cells.
Main Results:
- CAP37 activated endothelial protein kinase C in a dose- and time-dependent manner.
- CAP37 enhanced monocyte adhesion to the endothelium by upregulating ICAM-1 and PECAM-1.
- CAP37 promoted endothelial cell migration and was induced by inflammatory cytokines and LPS.
Conclusions:
- CAP37 plays a critical role in monocyte-endothelial cell interactions.
- CAP37 facilitates monocyte transmigration into tissues.
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