Journal of Applied Physiology, Vol 62, Issue 4 1521-1530, Copyright © 1987 by American Physiological Society

ARTICLES

Cationic neutrophil proteins increase transendothelial albumin movement

M. W. Peterson, P. Stone and D. M. Shasby

Neutrophils play a role in the development of pulmonary edema in many models of the adult respiratory distress syndrome, but the mechanism of their action is not completely understood. We asked whether two neutrophil secretory products, human neutrophil cationic protein (NCP) and human neutrophil elastase (HNE), would nonenzymatically alter the movement of albumin across a cultured endothelial monolayer. Both enzymes were inactivated by heating before use. HNE was additionally enzymatically inactivated with a chloromethylketone oligopeptide (CMK) inhibitor and with alpha 1-proteinase inhibitor (alpha 1-PI). Heated NCP, heated HNE, and CMK-complexed HNE all increased transendothelial albumin transfer. The cation protamine also increased albumin transfer across the endothelium and this increase was blocked by heparin. Alpha 1-PI and fetal bovine serum also prevented the cationic proteins from increasing albumin transfer. Using the release of lactate dehydrogenase as a marker of cytotoxicity, heated HNE was toxic to endothelial cells, heated NCP had only minimal toxicity, and protamine had no toxicity. Changes in endothelial cell shape with gap formation was seen after exposure to both heated HNE and heated NCP. Both the cytotoxicity associated with heated HNE and the cell shape changes associated with heated NCP and heated HNE could be blocked by heparin. These results suggest that in addition to neutrophil proteases and reactive O2 molecules, neutrophil-derived cationic proteins can directly and nonenzymatically contribute to edema formation during acute inflammation.

This article has been cited by other articles:

				J. Han, A. E. Woytowich, A. K. Mandal, and L. M. Hiebert Heparanase Upregulation in High Glucose-Treated Endothelial Cells Is Prevented by Insulin and Heparin Experimental Biology and Medicine, July 1, 2007; 232(7): 927 - 934. [Abstract] [Full Text] [PDF]

				S. D. Swain, T. W. Wright, P. M. Degel, F. Gigliotti, and A. G. Harmsen Neither Neutrophils nor Reactive Oxygen Species Contribute to Tissue Damage during Pneumocystis Pneumonia in Mice Infect. Immun., October 1, 2004; 72(10): 5722 - 5732. [Abstract] [Full Text] [PDF]

				J. R. Sanders, N. A. Pou, and R. J. Roselli Neutral and DEAE dextrans as tracers for assessing lung microvascular barrier permeability and integrity J Appl Physiol, July 1, 2002; 93(1): 251 - 262. [Abstract] [Full Text] [PDF]

				W. L. LEE and G. P. DOWNEY Leukocyte Elastase . Physiological Functions and Role in Acute Lung Injury Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 896 - 904. [Full Text] [PDF]

				C. B. S. Henry and B. R. Duling TNF-alpha increases entry of macromolecules into luminal endothelial cell glycocalyx Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2815 - H2823. [Abstract] [Full Text] [PDF]

				N. Gautam, H. Herwald, P. Hedqvist, and L. Lindbom Signaling via {beta}2 Integrins Triggers Neutrophil-dependent Alteration in Endothelial Barrier Function J. Exp. Med., May 30, 2000; 191(11): 1829 - 1840. [Abstract] [Full Text] [PDF]

				K. H. Ko, C. J. Lee, C. Y. Shin, M. Jo, and K. C. Kim Inhibition of mucin release from airway goblet cells by polycationic peptides Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L811 - L815. [Abstract] [Full Text] [PDF]