Increased expression of inflammatory cytokines and adhesion molecules by alveolar macrophages of human lung allograft recipients with acute rejection: Decline with resolution of rejection

Background: Alveolar macrophages (AM) are the major population in bronchoalveolar lavage (BAL) cells; we assessed their role in human lung allograft recipients by correlating the expression of adhesion molecules and inflammatory cytokines with clinical outcome of allograft. Methods: We obtained BAL samples from patients and enriched them for AM in plastic petri dish for 2 hours at 37°C in 5% CO₂. Expression of intercellular adhesion molecule-1 (ICAM-1, CD54), platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), and CD11c was assessed by flow cytometry using monoclonal antibodies. We assessed cytokine profile using Multi-Probe RNase protection assay. Results: Alveolar macrophages that express CD11c, CD31 and CD54 were increased in patients with either rejection or infection compared with those without rejection and infection. The difference in the percentage of AM expressing CD11c and CD31 between the rejection group and patients without rejection and infection group was statistically significant (CD11c, p < 0.01; CD31, p < 0.03). Interleukin (IL)-1α, IL-1β, IL-1 receptor antagonist (IL- 1Ra), and IL-6 expression was higher in the rejection group than in patients without rejection. Five out of 9 patients in the rejection group expressed high levels of IL-15 and tumor necrosis factor-α compared with patients without rejection and infection. The increased number of AM expressing adhesion molecules and elevated expression of cytokines observed during acute rejection declined to basal levels after successful treatment and resolution of rejection. Conclusion: This study demonstrates that lung allograft rejection is associated with increased expression of adhesion molecules and inflammatory cytokines by AM, which could facilitate mononuclear cell adhesion and extravasation contributing to the allograft injury in lung transplant recipients.