A novel CD8 molecule expressed by alveolar and peritoneal macrophages stimulates nitric oxide production

• Published in: The Journal of immunology (1950) Vol. 158; no. 4; pp. 1833 - 1840
• Main Authors: Hirji, N, Lin, TJ, Befus, AD
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.1997
• Subjects: Animals; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; CD8 Antigens - genetics; CD8 Antigens - physiology; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Male; Nitric Oxide - biosynthesis; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.4.1833

Macrophages play an essential role in host defense, and we have identified a novel CD8 molecule, on alveolar and peritoneal macrophages, that may be involved in regulating this function. Flow cytometric analysis of bronchoalveolar lavage from normal rats identified a large number of CD8-positive cells that could not be accounted for by T lymphocytes. Within the scatter profile region in which the majority of cells were alveolar macrophages (OX41; 89 +/- 1%), 63 +/- 5% of the cells stained positively for CD8alpha (OX8) and 52 +/- 3% for CD8beta (341). Double-staining of lavage cells confirmed the presence of CD8 on alveolar macrophages. Interestingly, flow cytometry showed differences between CD8 on alveolar macrophages and on T lymphocytes within the ligand binding domain for MHC class I. Reverse transcription-PCR analysis on FACS-enriched alveolar macrophages showed the presence of CD8alpha mRNA, determining that macrophages synthesize CD8. Further studies identified both the alpha (49 +/- 8%)- and beta (37 +/- 4%)-chains of CD8 on peritoneal lavage cells (86 +/- 3% macrophages (OX42, CD11b)). As with alveolar macrophages, there were differences within the ligand-binding domain of CD8 on peritoneal macrophages compared with T lymphocytes. Functional studies determined that anti-CD8alpha (OX8) stimulated a dose-dependent release of nitric oxide, indicating that CD8 can directly regulate macrophage function. Thus, macrophages express an unusual CD8 molecule that differs within its ligand-binding domain, compared with T lymphocytes, and these findings suggest hitherto unknown ligand(s) for CD8. These findings will lead to a greater understanding of macrophage function and regulation.