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Published ahead of print on April 15, 2004, doi:10.1165/rcmb.2003-0404OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 2, August 2004, 246-255

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Submitted on November 11, 2003
Revised on April 14, 2004

Role for Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM) in Macrophage Fc{gamma} Receptor Function

Steven M Albelda1*, Kelvin C Lau1, Paul Chien2, Zhen-Yu Huang2, Eugenia Arguiris1, Alyssa Bohen1, Jing Sun1, Jessica A Billet2, Melpo Christofidou-Solomidou1, Zena K Indik2, and Alan D Schreiber2

1 Department of Medicine, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 2 Department of Medicine, Hematology Division, University of Pennsylvania Medical Center, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: albelda{at}mail.med.upenn.edu.

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 TNF 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{gamma} Receptor-dependant phagocytosis and TNF release were significantly reduced in macrophages derived from PECAM-1 KO 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{gamma} receptors on alveolar macrophages.




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