This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Q. Articles by Doerschuk, C. M. Search for Related Content PubMed PubMed Citation Articles by Wang, Q. Articles by Doerschuk, C. M.

Lung Microvascular and Arterial Endothelial Cells Differ in Their Responses to Intercellular Adhesion Molecule-1 Ligation

Division of Integrative Biology, Department of Pediatrics, Rainbow Babies and Children's Hospital and Case Western Reserve University, Cleveland, Ohio; and Department of Pharmacology, University of South Alabama, Mobile, Alabama

Correspondence and requests for reprints should be addressed to Claire M. Doerschuk, M.D., Rainbow Babies and Children's Hospital and Case Western Reserve University, Room 787, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: cmd22{at}po.cwru.edu

Neutrophil adherence to tumor necrosis factor- (TNF-)–treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)–dependent signaling events. This study determined whether similar changes occurred in rat PMECs and whether rat pulmonary arterial endothelial cells (PAECs) responded differently. Neutrophil adherence induced an increase in the formation of F-actin and in the apparent stiffness of TNF-–treated rat PMECs. These responses, however, were absent in PAECs. To determine the mechanisms underlying these differences, ICAM-1–mediated signaling events were compared. Upregulation of ICAM-1 by TNF- and redistribution of ICAM-1 induced by cross-linking antibodies were similar in both cell types. However, neutrophil adherence induced production of reactive oxygen species only in PMECs and not in PAECs. Moreover, phosphorylation of p38 mitogen-activated protein kinase induced by ICAM-1 cross-linking occurred only in PMECs and not in PAECs. This increase in p38 phosphorylation in PMECs was inhibited by allopurinol, a xanthine oxidase inhibitor. These data demonstrated that whereas TNF- upregulated ICAM-1 and ICAM-1 cross-linking induced a similar redistribution of ICAM-1 on the endothelial cell surface, ICAM-1 ligation initiated p38 activation and cytoskeletal rearrangements only in PMECs and not in PAECs. Thus, neutrophil adhesion through ICAM-1 induced signaling events leading to cytoskeletal changes only in PMECs, the site of neutrophil emigration and edema formation, and not in PAECs.

Key Words: intercellular adhesion molecule-1 • signaling • lung • endothelial cell

This article has been cited by other articles:

				A. A. Birukova, N. Moldobaeva, J. Xing, and K. G. Birukov Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L612 - L623. [Abstract] [Full Text] [PDF]

				A. M. Kaynar, A. M. Houghton, E. H. Lum, B. R. Pitt, and S. D. Shapiro Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 53 - 60. [Abstract] [Full Text] [PDF]

				R. Sumagin and I. H. Sarelius A role for ICAM-1 in maintenance of leukocyte-endothelial cell rolling interactions in inflamed arterioles Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2786 - H2798. [Abstract] [Full Text] [PDF]

				J. Reutershan, R. Stockton, A. Zarbock, G. W. Sullivan, D. Chang, D. Scott, M. A. Schwartz, and K. Ley Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration Am. J. Respir. Crit. Care Med., May 15, 2007; 175(10): 1027 - 1035. [Abstract] [Full Text] [PDF]

				R. Sumagin and I. H. Sarelius TNF-{alpha} activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2116 - H2125. [Abstract] [Full Text] [PDF]

				S. Muro, T. Dziubla, W. Qiu, J. Leferovich, X. Cui, E. Berk, and V. R. Muzykantov Endothelial Targeting of High-Affinity Multivalent Polymer Nanocarriers Directed to Intercellular Adhesion Molecule 1 J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1161 - 1169. [Abstract] [Full Text] [PDF]

				N. Miyao, Y. Suzuki, K. Takeshita, H. Kudo, M. Ishii, R. Hiraoka, K. Nishio, T. Tamatani, S. Sakamoto, M. Suematsu, et al. Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1059 - L1068. [Abstract] [Full Text] [PDF]

				R. Arnold and W. Konig Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression J. Immunol., June 1, 2005; 174(11): 7359 - 7367. [Abstract] [Full Text] [PDF]

				H. M. Razavi, L. F. Wang, S. Weicker, M. Rohan, C. Law, D. G. McCormack, and S. Mehta Pulmonary Neutrophil Infiltration in Murine Sepsis: Role of Inducible Nitric Oxide Synthase Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 227 - 233. [Abstract] [Full Text] [PDF]

				R. S. Frey and A. B. Malik Oxidant signaling in lung cells Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L1 - L3. [Full Text] [PDF]

				J. Agorreta, M. Garayoa, L. M. Montuenga, and J. J. Zulueta Effects of Acute Hypoxia and Lipopolysaccharide on Nitric Oxide Synthase-2 Expression in Acute Lung Injury Am. J. Respir. Crit. Care Med., August 1, 2003; 168(3): 287 - 296. [Abstract] [Full Text] [PDF]

				M. J. Tobin Critical Care Medicine in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 294 - 305. [Full Text] [PDF]