The expression of molecules of the CD11/CD18 cell surface adhesion glycoprotein family and HLA/DR antigen was studied on peripheral blood monocytes (PBM) and alveolar macrophages (AM) in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), and extrinsic allergic alveolitis (EAA). Patients with these interstitial lung diseases showed increased numbers of macrophages in BAL fluid. This was probably caused by an increased influx of PBM to the alveoli since the numbers of cells with a monocytic morphology were also significantly increased in BAL samples from patients with interstitial lung disease, most prominently in IPF and EAA. The increased influx of PBM into the alveoli in patients with interstitial lung diseases was not reflected by an increased expression of the CD11/CD18 leukocyte function antigens on PBM. In healthy volunteers as well as in those with sarcoidosis, IPF, and EAA, the percentages of AM positive for CD11b (the C3bi complement receptor) and CD11c were lower than among PBM. This indicates that the expression of these cell surface adhesion molecules is downregulated during maturation and migration of PBM to the alveoli. The absolute numbers of AM positive for CD11b were increased in BAL fluid of IPF and EAA patients compared to healthy volunteers. EAA patients also showed increased absolute numbers of AM positive for CD11a and CD11c. This differentially increased expression of these leukocyte function antigens on AM suggests the influence of locally produced cytokines.

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During the last few years substantial evidence has been raised for the involvement of inflammatory processes in the pathophysiology of Chronic Obstructive Pulmonary Diseases (COPD) and asthma. Concerning pulmonary diseases we are particularly interested in the modulatory function of the alveolar macrophage (AM). This cell plays a predominant role by exhibiting its typical inflammation-related properties as phagocytosis, cytotoxicity, antigen-presentation and the production of pro-and antiinflammatory mediators, proteolytic enzymes and oxygen-radicals. Many of these functions are known to be inhibited by increasing hatracellular levels of cyclic AMP (c-AMP), a second messenger formed through the activation of adenyl cyclase. In our research, we examine the modulation of the adenyl cyclase system in alveolar macrophages with a special interest to the role of this cell in COPD and asthma. In a previous study in our laboratory, using an animal model for human allergic asthma, we observed an increase in the sensitivity of the adenyl cyclase system in antigen chal!enged AMs, probably the result of changes which have occured in this system on the level of the regulatory bindh~g protehls (1). In the presented study we examined the effects of some inflammatory mediators and fl-adrenergic drugs on the adenyl cyclase activity of normal human alveolar macrophages. AMs were obtained by broncho alveolar lavage (BAL) of 29 healthy smolcing (n ffi 25) and non-smoking (n = 4), male (n -4) and female (n = 25) subjects; mean age was 34:1:9.4 years. All subjects did not receive any medication during three weeks prior to BAL and had no history of pulmonary disorders. We did not exclude smoking subjects from this study as similar results were found between smokers and non-smokers in basal c-AMP levels (smokers: 2.47:1:0.08 vs. non-smokers: 2.94 + 0.45 pmol c-AmP/1 • 10 6 cells) and c-AMP response clue to agonist-exposure; the viability of the cells recovered from BAL was 90.9 + 0.88% whereas the majority (> 95 ~) consisted of AMs as differentiated by May-Griinwald-Giemsa staining. The inflammatory mediators prostaglandin E2 (PGE2), prostacyclin (DC-PGI2, a stable analogue) and histanfine induced a close-dependent increase of basal c-AMP levels in AMs (PGE2: 379-61%, DC-PGI2:231 _+ 51 ~, histamine: 115:1: 35?o; dose-range from 2~8-10 -s -2.8-10 -4 M) whereas platelet activating factor (PAF) had no effect on AM adenyl cyclase (dose-range from 1-10 -12-1.10 -5 M). Using the selective histaminergic receptor antagonists Mepyramine and Cimeticline (1 • 10-5 M), it was shown that the effect of histamine was mediated via H2-receptors. The non-selective and full ~-adrenergic ago.nist isoprena!ine iaduced an increase of basal c-AMP levels of 175 _4-36 ~ whereas the/32-selective adrenerl!;ic agonist salbutamol induced an increase of only 76 _ 10 %. Again, using fl-adrenoceptor antagonists, it was :~;hown that the effects of isoprenaline and salbutamol on AM adenyl cyclase were mediated through fl2-receptors. These results show that the inflamma...

Among patients with asthma or chronic obstructive pulmonary diseases the response to glucocorticoids varies considerably. To investigate the possible relationship between clinical response and number of glucocorticoid receptors in alveolar macrophages or their KD value a micro receptor assay was developed. Assay conditions were adjusted because of receptor occupancy by endogenous or therapeutically used glucocorticoids and high aspecific binding.