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Human pulmonary macrophages utilize prostaglandins and transforming growth factor β 1 to suppress lymphocyte activation
Author(s) -
Roth Michael D.,
Golub Sidney H.
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.53.4.366
Subject(s) - in vitro , transforming growth factor , lymphocyte , biology , macrophage , alveolar macrophage , immunology , microbiology and biotechnology , pharmacology , biochemistry
The ability to activate peripheral blood lymphocytes (PBLs) in vitro with interleukin‐2 (IL‐2) is suppressed by the presence of autologous human pulmonary alveolar macrophages (AMs). AMs suppress both IL‐2‐induced proliferation and the induction of lympho‐ kine‐activated killer cell (LAK) activity in a dose‐ dependent manner (79 ±6% suppression of LAK activity at a 0.25:1 AM/PBL ratio). Increasing the IL‐2 concentration increased baseline LAK activity but did not prevent AM‐mediated suppression. At least two different mechanisms of suppression were observed, one diffusible in nature and the other contact dependent. Indomethacin prevented the component of inhibition that diffused across porous polycarbonate membranes, indicating prostaglandins as the diffusible inhibitor. In contrast, indomethacin had no effect when added alone into conventional AM‐ PBL cocultures, but a combination of indomethacin and anti‐transforming growth factor β 1 (TGF‐β 1 ) antibody did prevent inhibition. This result suggests that TGF‐ß1 acts as an additional contact‐dependent inhibitor. PBLs that were rendered unresponsive to IL‐2 completely recovered their responsiveness within 4 days after removing AMs from the coculture. These features suggest that pulmonary macrophages have multiple mechanisms for locally suppressing IL‐2 responses and lymphocyte activation.