Monocyte Chemoattractant Protein‐1 (MCP‐1) released from alveolar macrophages mediates the systemic inflammation of alveolar hypoxia

Abstract

Alveolar hypoxia (AH) produces widespread systemic inflammation in rats. The inflammation is initiated by a circulating mediator released from alveolar macrophages (AMØ) activated by the low alveolar PO2. The mediator(s) induces mast cell degranulation (MCD) with release of inflammatory agents. Recent data suggest MCP‐1 as a mediator. If this is true: 1) Circulating levels of MCP‐1 should increase with AH in intact rats; 2) AMØ depletion should prevent this increase; 3) Plasma from intact AH rats, but not AMØ‐depleted AH rats, should produce MCD; 4) MCP‐1 added to normoxic plasma or AMØ supernatant should produce MCD.AH (FIO2 = 0.1 for 60 min) produced a rapid (5 min) and sustained 6‐fold increase in plasma MCP‐1 of intact rats. 2) This increase was abolished by AMØ depletion by tracheal instillation of clodronate‐containing liposomes. 3) Mast cell immersion in plasma from AH intact rats, but not in plasma from AMO‐depleted rats, produced MCD. 4) Dose‐dependent MCD occurred when MCP‐1 was added to normoxic AMØ supernatant or rat plasma, but not when added to normoxic culture medium.ConclusionsIn the intact, conscious rat, AH induces release of MCP‐1 from AMØ, which, in turn, produces MCD and initiates systemic inflammation of AH. To induce MCD, MCP‐1 requires another substance(s) which is present in both normoxic plasma and normoxic AMØ supernatant.Supported by NIH HL39443‐18, AHA 0815652G and APS Frontiers in Biology