Environmental Health Perspectives 105, Supplement 5, September 1997: Article by Holian et al.

Environmental Health Perspectives 105, Supplement 5, September 1997

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Asbestos and Silica-induced Changes in Human Alveolar Macrophage Phenotype

Andrij Holian, ¹ Margaret O. Uthman, ² Tatiana Goltsova, ² Steven D. Brown, ¹ and Raymond F. Hamilton Jr. ¹

¹ Departments of Internal Medicine and ² Pathology, University of Texas Houston Health Science Center, Houston, Texas

Abstract
The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1 ⁺ phenotype (inducer or immune activator macrophages) and decreased the RFD1 ⁺ RFD7 ⁺ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation. -- Environ Health Perspect 105(Suppl 5):1139-1142 (1997)

Key words : RFD1, RFD7, inflammation, fibrosis, apoptosis

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York.Manuscript received at EHP 26 March 1997; accepted 2 July 1997.

This work was supported by National Institutes of Health grants ES-04804 and M01-RR-02558.

Address correspondence to Dr. A. Holian, 1.276 MSB, Department of Internal Medicine. University of Texas Houston Health Science Center, 6431 Fannin, Houston, TX 77030. Telephone: (713) 500-7955. Fax: (713) 500-6829. E-mail: aholian@heart.med.uth.tmc.edu

Abbreviations used: AM, alveolar macrophage(s); BSA, bovine serum albumin; CHR, chrysotile; CNT, control; CRO, crocidolite; MoAb, monoclonal antibodies; PBS, phosphate-buffered saline; SIL, crystalline silica; and TIO, titanium dioxide; WOL, wollastonite.

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Last Update: October 23, 1997