Phenotypic and functional modulation of normal human alveolar macrophages by histamine.
Alveolar macrophages (AM) play a regulatory role in asthma. AM from asthmatics are activated, release increased amounts of cytokines, and express higher levels of the low affinity receptor for IgE (Fc epsilon RIIb/CD23b) and receptors for adhesion molecules. The bronchial microenvironment may modulate the phenotypic and functional characteristics of AM. On AM from normal subjects, the effects of histamine were studied on the expression of adhesion molecules (LFA-1, ICAM-1) and CD23b as well as on the release of fibronectin. The expression of LFA-1, ICAM-1, and CD23b was examined by immunocytochemistry using the alkaline phosphatase-anti-alkaline phosphatase technique. The expression of CD23b mRNA was studied by in situ hybridization. The release of fibronectin was measured by enzyme immunoassay. We found that histamine induced in a dose- and time-dependent fashion a significant increase of AM expressing the three membrane markers and a significant increase in the release of fibronectin. The maximum effect of histamine was observed after an incubation of 12 to 24 h and a dose of 1 microM. The histamine effects were specific, since they were significantly inhibited by an H1-blocker, pyrilamine, used at a concentration of 10 microM. The effect of an H2-blocker (ranitidine, concentration of 10 microM) was inconstant. Cycloheximide blocked the histamine effects, suggesting that it requires protein synthesis for its action. This study provides an in vitro model of cellular interaction between mast cells and AM, which might be relevant in the airway inflammation in asthma.
Vignola
A M
AM
Clinique des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France.
Chanez
P
P
Paul-Lacoste
P
P
Paul-Eugène
N
N
Godard
P
P
Bousquet
J
J
D000328:Adult; D000368:Aged; D001249:Asthma / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011738:Pyrilamine / Q000494:pharmacology; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D005353:Fibronectins; D016169:Lymphocyte Function-Associated Antigen-1; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine; D003513:Cycloheximide; D011738:Pyrilamine