PARTICLE OPSONIZATION AND LUNG MACROPHAGE CYTOKINE RESPONSE - IN-VITRO AND IN-VIVO ANALYSIS

Inhaled inert particles and organisms cause a spectrum of pulmonary re sponses, ranging from minimal changes to marked acute inflammation. Du ring ingestion and clearance of such particles, alveolar macrophages ( AM) can initiate pulmonary inflammation by production of TNF and neutr ophil chemoattractant cytokines. We tested the role of opsonization in determining the AM response to ingestion of inert particles in vitro and in vivo. As measures of AM activation after phagocytosis in vitro, we measured release of TNF and mRNA expression for the platelet-facto r 4 family neutrophil chemoattractants, KC and macrophage-inflammatory protein-2 (MIP-2). Using albumin-coated fluorescent latex particle as phagocytic targets, we found a marked release of TNF by AM ingesting particles opsonized with antialbumin IgG, although uptake of similar n umbers of unopsonized particles caused little or no release (e.g., 464 8 +/- 1147 pg/ml, opsonized beads vs 576 +/- 205 unopsonized, 10:1 par ticle:cell ratio, n = 4, mean +/- SD). Flow cytometry confirmed equal uptake of the two particle types. Northern analysis of AM mRNA showed marked induction of KC and MIP-2 mRNA after ingestion of opsonized par ticles only. Instillation of opsonized particles into hamster lungs ca used a marked neutrophil influx, although unopsonized particles did no t. TNF was elevated in lavage fluid after instillation of opsonized pa rticles, but not after unopsonized beads (92.7 +/- 136 pg/ml opsonized , n = 7 vs 1.3 +/- 3.6 unopsonized, n = 6). KC and MIP-2 mRNA were ind uced in lavaged cells after instillation of opsonized but not after un opsonized particles or vehicle control. The nature of particle interac tion with the AM surface during phagocytosis determines the subsequent AM response. Although many unopsonized inert particles are ingested w ith minimal AM activation, specific opsonization of pathogens or non-s pecific adsorption of Ig onto other particles may activate AM and lead to pulmonary inflammation.