Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio; Physiology Program, Harvard School of Public Health, Boston, Massachusetts; Herman B. Wells Center for Pediatric Research and the Section of Pulmonology and Intensive Care, the Departments of Pediatrics and Anatomy, Indiana University, Indianapolis, Indiana; and Pulmonary Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31)
is an adhesion molecule believed to mediate transendothelial
migration of neutrophils and other leukocytes after CD11/CD18-mediated
adhesion. Our study evaluated the role of PECAM-1 in neutrophil
emigration across the pulmonary capillaries and the bronchial
microvasculature using blocking anti–PECAM-1 antibodies
in mice and rats. Neutrophil emigration was induced by
Escherichia coli, a stimulus eliciting CD11/CD18-dependent emigration, or
Streptococcus pneumoniae, a stimulus inducing CD11/CD18-independent
emigration. Although anti–PECAM-1 antibodies partially
inhibited glycogen-induced neutrophil emigration into the peritoneum,
neutrophil emigration across either the pulmonary capillaries
or the bronchial microvasculature in response to either
E. coli or
S. pneumoniae was not prevented when the function of PECAM-1
was inhibited in either mice or rats. There was also no increase
in the number of intravascular neutrophils within the bronchial
vessels after treatment with anti–PECAM-1 antibody. These
studies indicate that either CD11/CD18-dependent or -independent
adhesion pathways may lead to PECAM-1–independent transendothelial
migration through the pulmonary or the bronchial endothelium.
Key Words: rodent • lung • neutrophils • infectious immunity-bacteria • adhesion molecules
Neutrophil emigration into the alveolar space is one of the
hallmarks of acute bacterial pneumonia (
1). During bacterial
pneumonia, neutrophils marginate within the microvasculature,
adhere to endothelial cells, and transmigrate between endothelial
cells into the alveolar space. Each step in this process is
mediated by specific mechanisms and molecules.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is a transmembrane protein and a member of immunoglobulin (Ig) gene superfamily structurally related to intercellular adhesion molecule-1 (2, 3). It is constitutively expressed at the junctions between endothelial cells and on the surface of leukocytes and platelets (2–5). Roles for PECAM-1 in modulating leukocyte adhesion and migration, angiogenesis, and thrombosis have been described (5–9). PECAM-1 is also an intracellular signaling molecule, and recent studies have suggested it is a member of the immunoreceptor tyrosine-based inhibitory motif subfamily of the Ig superfamily (3). Many studies have demonstrated that it plays a critical role in the transendothelial migration of neutrophils (10). In vitro studies show that anti–PECAM-1 antibody or soluble PECAM-1 inhibits neutrophil transmigration across the endothelium activated by tumor necrosis factor (TNF)- (11). Similarly, in vivo studies show that anti–PECAM-1 antibody blocks neutrophil emigration in chemical-induced peritonitis (12–14).
PECAM-1 is expressed constitutively on pulmonary arterial, capillary, and venular endothelium, yet many questions regarding the role that this highly expressed cell adhesion molecule plays in pulmonary inflammation remain. An increase in PECAM-1 expression has been reported in mice exposed to 100% oxygen for 3 to 4 days, although the functional significance of this change was not studied (15). The only functional studies, to our knowledge, have been by Vaporciyan and colleagues who showed that IgG immune complex-induced lung injury, a process requiring neutrophils, interleukin (IL)-1, TNF-
作者：
Sadatomo Tasaka, Lan Qin, Ariko Saijo, Steven M. A 2007-5-14