This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0363OCv1 37/2/248    most recent 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 Hollingsworth, J. W. Articles by Schwartz, D. A. Search for Related Content PubMed PubMed Citation Articles by Hollingsworth, J. W. Articles by Schwartz, D. A.

CD44 Regulates Macrophage Recruitment to the Lung in Lipopolysaccharide-Induced Airway Disease

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham; National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and Divisions of Pulmonary and Vascular Biology and Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas

Correspondence and requests for reprints should be addressed to J. W. Hollingsworth, M.D., Division of Pulmonary and Critical Care Medicine, DUMC 3136, Duke University Medical Center, Durham, NC 27710. E-mail: holli017{at}mc.duke.edu.

LPS from bacteria is ubiquitous in the environment and can cause airway disease and modify allergic asthma. Identification of gene products that modulate the biologic response to inhaled LPS will improve our understanding of inflammatory airways disease. Previous work has identified quantitative trait loci for the response to inhaled LPS on chromosomes 2 and 11. In these regions, 28 genes had altered RNA expression after inhalation of LPS, including CD44, which was associated with differences in both TNF- levels and neutrophil recruitment into the lung. It has previously been shown that CD44 can modulate macrophage recruitment in response to Mycobacterium tuberculosis, as well as clearance of neutrophils after lung injury with both bleomycin and live Escherichia coli bacteria. In this study, we demonstrate that the biologic response to inhaled LPS is modified by CD44. Macrophages failed to be recruited to the lungs of CD44-deficient animals at all time points after LPS exposure. CD44-deficient macrophages showed reduced motility in a Transwell migration assay, reduced ability to secrete the proinflammatory cytokine TNF-, reduced in vivo migration in response to monocyte chemotactic protein-1, and diminished adhesion to vascular endothelia in the presence of TNF-. In addition, CD44-deficient animals had 150% fewer neutrophils at 24 h and 50% greater neutrophils 48 h after LPS exposure. These results support the role of CD44 in modulating the biologic response to inhaled LPS.

Key Words: lung • environment • tlr4 • hyaluronan • endotoxin

CLINICAL RELEVANCE CD44 regulates macrophage accumulation in the lungs of mice exposed to inhaled endotoxin. CD44-dependent defects in macrophage migration are, in part, due to reduced endothelium adhesion. CD44 plays an important role in pulmonary innate immunity.

 

This article has been cited by other articles:

				J A Frank, J-F Pittet, C Wray, and M A Matthay Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade Thorax, February 1, 2008; 63(2): 147 - 153. [Abstract] [Full Text] [PDF]