LFA-1 and ICAM-1 in homotypic aggregation of rat alveolar macrophages: organic dust-mediated aggregation by a non-protein kinase C-dependent pathway.
We have examined the role of cell adhesion molecules in the homotypic aggregation of rat alveolar macrophages after exposure to wool and grain dusts. Molecules such as bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) can upregulate adhesion molecules, resulting in aggregation of lymphocytes. In rats treated intratracheally with an inspirable sample of wool dust collected from the air of British wool textile mills, and sieved grain dust, aggregates of macrophages were present in the bronchoalveolar lavage (BAL). Our hypothesis was that substances present on the dust surface could activate and upregulate adhesion molecules of the CD11/CD18 complex on the BAL cells and account for the aggregates. Macrophages from untreated rats form aggregates in vitro, which averaged 19 cells/aggregate; when treated with both wool and grain dusts, this rose to 25 and 24 cells/aggregate, respectively. LPS, PMA, and the proinflammatory cytokine tumor necrosis factor (TNF) also caused increases in aggregate size. Staurosporine, an inhibitor of protein kinase C (PKC), reduced the number of cells per aggregate from 35 cells/aggregate in LPS- and PMA-treated macrophages to 18 cells/aggregate, the same as untreated. In contrast, staurosporine had no effect in reducing the size of aggregates produced by the organic dusts. Removal of divalent cations, which are essential for maintaining integrin stability and PKC activity, resulted in complete abolition of aggregate formation. Treatment with monoclonal antibodies to lymphocyte function-associated antigen-1 (LFA-1) alpha and beta and intercellular adhesion molecule-1 (ICAM-1) resulted in the inhibition of aggregate formation in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Brown
D M
DM
Institute of Occupational Medicine, Rayne Laboratory, University of Edinburgh, City Hospital, United Kingdom.
Dransfield
I
I
Wetherill
G Z
GZ
Donaldson
K
K
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects; D004391:Dust; D002523:Edible Grain; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014935:Wool
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D004391:Dust; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate