Pulmonary macrophages: Phenomena associated with the particle ``overload`` condition

Conference · Sat May 01 04:00:00 EDT 1993

OSTI ID:10159778

Lehnert, B E; Sebring, R J ^[1]; Oberdoerster, G ^[2]

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1. Los Alamos National Lab., NM (United States)
2. Rochester Univ., NY (United States)

Numerous lines of evidence support the generalization that alveolar macrophage (AM)-mediated particle clearance, or the transport of particle-containing AM from the alveoli out of the lung via the mucociliary apparatus, is a prominent mechanism that determines the pulmonary retention characteristics of relatively insoluble particles. Studies have also shown that the alveolar deposition of excessive burdens of particles with even low intrinsic cytotoxicity can result in impairments of the AM-mediated panicle clearance mechanism and the development of pathologic disorders including pulmonary fibrosis and lung cancer, at least in the lungs of rats. We briefly review evidence consistent with the idea that the high volumetric loads of particles contained in AM during particle overload conditions underlies their inabilities to translocate from the lung. Using a condition of particle overload brought about by subchronic exposure of rats to ultra-fine titanium dioxide as an experimental model, we have obtained ultrastructural and other evidence that indicates an association between particle overload and: The occurrence of aggregates of particle-containing AM in alveoli, Type II cell hyperplasia in alveoli that contain the AM aggregates, a loss in patent pores of Kohn in alveoli that contain the AM aggregates and show Type II cell hyperplasia, the interstitialization of particles at the sites where these phenomena collectively occur, and the development of fibrosis in alveolar regions where particle interstitialization occurs. The loss of pores of Kohn in the alveoli that contain aggregates of particle-laden AM suggests that these interalveolar pores normally serve as passageways through which AM may migrate to neighboring alveoli as they perform their function of phagocytizing particles that have deposited on the alveolar surface. The pores of Kohn also serve as short-cut pathways for AM to reach the mucociliary apparatus from more distal alveoli.

• Research Organization: Los Alamos National Lab., NM (United States)
• Sponsoring Organization: USDOE, Washington, DC (United States)
• DOE Contract Number: W-7405-ENG-36
• OSTI ID: 10159778
• Report Number(s): LA-UR--93-1164; CONF-9303155--2; ON: DE93012652
• Country of Publication: United States
• Language: English

Related Subjects

550900
560300
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL FUNCTIONS
CHEMICALS METABOLISM AND TOXICOLOGY
ELECTRON MICROSCOPY
INHALATION
LUNG CLEARANCE
LUNGS
MACROPHAGES
PARTICULATES
PATHOLOGY
PHYSIOLOGY
TITANIUM OXIDES