The IL-4/13-induced production of M2 chemokines by human lung macrophages is enhanced by adenosine and PGE2.

BACKGROUND AND PURPOSE: Lung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E2 (PGE2) affected the interleukin (IL)-4- and IL-13-induced release of M2a chemokines (CCL13, CCL17, CCL18, and CCL22) by human LMs. EXPERIMENTAL APPROACH: Primary macrophages isolated from resected human lungs were incubated with NECA, PGE2, roflumilast, or vehicle and stimulated with IL-4 or IL-13 for 24 h. The levels of chemokines and PGE2 in the culture supernatants were measured using ELISAs and enzyme immunoassays. KEY RESULTS: Exposure to IL-4 (10 ng/mL) and IL-13 (50 ng/mL) was associated with greater M2a chemokine production but not PGE2 production. PGE2 (10 ng/mL) and NECA (10-6 M) induced the production of M2a chemokines to a lesser extent but significantly enhanced the IL-4/IL-13-induced production of these chemokines. At either a clinically relevant concentration (10-9 M) or at a concentration (10-7 M) that fully inhibited phosphodiesterase 4 (PDE4) activity, roflumilast did not increase the production of M2a chemokines and did not modulate their IL-13-induced production, regardless of the presence or absence of PGE2. CONCLUSIONS: NECA and PGE2 enhanced the IL-4/IL-13-induced production of M2a chemokines. The inhibition of PDE4 by roflumilast did not alter the production of these chemokines. These results contrast totally with the previously reported inhibitory effects of NECA, PGE2, and PDE4 inhibitors on the lipopolysaccharide-induced release of tumor necrosis factor alpha and M1 chemokines in human LMs.

First use of imlifidase desensitization in a highly sensitized lung transplant candidate: a case report.

Lung transplant candidates who are highly sensitized against human leucocyte antigen present an ongoing challenge with regards to finding immunologically acceptable donors. Desensitization strategies aimed at reducing preformed donor-specific antibodies have a number of limitations. Imlifidase, an IgG-degrading enzyme derived from Streptococcus pyogenes, is a novel agent that has been used to convert positive crossmatches to negative in kidney transplant candidates, allowing transplantation to occur. We present the first case of imlifidase use for antibody depletion in a highly sensitized lung transplant candidate who went on to undergo a successful bilateral lung transplant.