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Role for Platelet-Endothelial Cell Adhesion Molecule-1 in Macrophage Fc Receptor Function

Pulmonary, Allergy, and Critical Care Division, and Hematology Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

Address correspondence to: Steven M. Albelda, M.D., 421 Curie Blvd., BRBII/III, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. E-mail: albelda{at}mail.med.upenn.edu

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) (CD31), a 130-kD transmembrane glycoprotein that functions in adhesion and signaling, is thought to play a role in some forms of leukocyte transmigration. In the lung, PECAM-1 is highly expressed, yet there have been few studies examining its role in pulmonary pathology. We therefore examined the inflammatory response (measured by bronchoalveolar lavage cell counts and protein content) after several types of lung injury in wild-type and PECAM-1 knockout mice. Consistent with studies in other organs, instillation of an endothelial stimulant (interleukin-1) was PECAM-1–dependent. In contrast, we noted that three other forms of acute lung injury (acid aspiration, adenoviral instillation, and tumor necrosis factor instillation) were completely PECAM-1–independent. Interestingly, in situ immune complex deposition injury, another complex lung disease, was also PECAM-1–dependent. This surprising finding was investigated in more detail and found to be due to a defect in macrophage activation, and not to a blockade of leukocyte transmigration. Experiments in bone marrow chimeric mice as well as ex vivo data demonstrated that Fc receptor–dependent phagocytosis and tumor necrosis factor release were significantly reduced in macrophages derived from PECAM-1 knockout mice. Although PECAM-1 may not be required for transmigration of leukocytes into the alveolar space in many forms of complex lung inflammation, it is important in the function of Fc receptors on alveolar macrophages.

Abbreviations: bronchoalveolar lavage, BAL • BAL fluid, BALF • bovine serum albumin, BSA • IgG-sensitized erythrocytes, EA • enzyme-linked immunosorbent assay, ELISA • immune complex deposition-induced injury, ICD • interleukin, IL • immunoreceptor tyrosine-based activation motif, ITAM • knockout, KO • lipopolysaccharide, LPS • phosphate-buffered saline, PBS • polymerase chain reaction, PCR • platelet-endothelial cell adhesion molecule-1, PECAM-1 • red blood cells, RBCs • tumor necrosis factor, TNF • white blood cells, WBCs • wild-type, WT

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