Increased adherence of monocytes to fibronectin in bronchiectasis. Regulatory effects of bacterial lipopolysaccharide and role of CD11/CD18 integrins.
Regulated adherence of monocytes to extracellular matrix is a prerequisite for accumulation of mononuclear phagocytes during pulmonary infection and inflammation. We have obtained monocytes from patients with an inflammatory lung disease (bronchiectasis) and from control subjects and have compared their adherence to fibronectin. Spontaneous adherence of monocytes from the control subjects was 20 +/- 2%, whereas that of patients' cells was markedly higher and correlated with the severity of airway inflammation: 65 +/- 5% and 40 +/- 8% in patients with purulent and mucoid sputum, respectively. Endotoxin and cytokines from areas of airway disease are likely to be responsible for the observed monocyte activation, since: (1) endotoxin was detectable in all of the patients but in none of the control subjects; (2) LPS produced a dose-related increase in adherence of normal monocytes in vitro (maximal 65 +/- 2% adherence at 1 microgram/ml of LPS); (3) recombinant cytokines and LPS produced additive effects on monocyte adherence in vitro. The adherence of the patients' monocytes to fibronectin was substantially mediated by CD11/CD18 integrins, via both RGD-dependent and RGD-independent mechanisms. These data indicate that signals arising from foci of infection and inflammation can influence the adherence of monocytes, and they are likely to be determinants of the accumulation of mononuclear phagocytes in the lungs of patients with bronchiectasis.
Owen
C A
CA
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, United Kingdom.
Campbell
E J
EJ
Hill
S L
SL
Stockley
R A
RA
D000328:Adult; D000368:Aged; D001987:Bronchiectasis / Q000097:blood / Q000276:immunology*; D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D005353:Fibronectins / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D004731:Endotoxins; D005353:Fibronectins; D016023:Integrins; D008070:Lipopolysaccharides