Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis.
Activation of human neutrophils (PMN) is accompanied by rapid upregulation of CR1, the C3b receptor, and CR3, the iC3b receptor, which also serves as the PMN's major adherence protein. This is necessary for migration and phagocytosis, but the extent of expression of these proteins on PMN at inflammatory sites has not been determined. We used monoclonal antibodies and flow cytometry to assess CR1 and CR3 expression on PMN in bronchoalveolar lavage (BAL) fluid of cystic fibrosis (CF) patients chronically infected with pseudomonas and in sterile joint fluid of arthritis patients. Resting peripheral blood PMN from these patients and normals expressed similar low levels of CR1 and CR3, and the patients' PMN increased CR1 and CR3 expression normally when stimulated in vitro. CR3 expression on CF BAL PMN was 90 +/- 12% of that on the same patient's blood cells stimulated in vitro with FMLP. In contrast, CR1 expression on BAL PMN was only 27 +/- 8% of that on stimulated blood cells. Similar results were obtained for joint PMN. This pattern could be reproduced in vitro by treating FMLP-stimulated blood cells with BAL supernatants or with pseudomonas or PMN elastase. The serine protease inhibitors, PMSF and alpha 1-antitrypsin prevented the lavage supernatant from reducing CR1 expression, while metalloprotease inhibitors had no effect. Treatment of PMN with elastase in vitro decrease their ability to kill opsonized Pseudomonas aeruginosa. These results suggest that PMN at inflammatory sites have maximally upregulated expression of their complement receptors, but that CR1 is then cleaved by proteolysis in situ. Although not related to the basic defect in CF, this may interfere with efficient phagocytosis and contribute to the CF patient's inability to eradicate chronic lung infection.
Berger
M
M
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Sorensen
R U
RU
Tosi
M F
MF
Dearborn
D G
DG
Döring
G
G
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D011552:Pseudomonas Infections / Q000150:complications / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D011951:Receptors, Complement / Q000378:metabolism*; D015854:Up-Regulation
D011480:Protease Inhibitors; D011951:Receptors, Complement; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010196:Pancreatic Elastase